Real-time in vivo dosimetry in high dose rate prostate brachytherapy

Background and purpose: Single fraction treatments of 15 Gy or 19 Gy are common in HDR prostate brachytherapy. In vivo dosimetry (IVD) is therefore important to ensure patient safety. This study assesses clinical IVD and investigates error detection thresholds for real-time treatment monitoring. Materials and methods: IVD was performed for 40 treatments planned using intra-operative trans-rectal ultrasound (TRUS) with a MOSFET inserted into an additional needle. Post-treatment TRUS images were acquired for 20 patients to assess needle movement. Monte Carlo simulations of treatment plans were performed for 10 patients to assess impact of heterogeneities. Per-needle and total plan uncertainties were estimated and retrospectively applied to the measured data as error detection thresholds. Results: The mean measured dose was −6.4% compared to prediction (range + 5.1% to −15.2%). Needle movement and heterogeneities accounted for −1.8% and −1.6% of this difference respectively (mean values for the patients analysed). Total plan uncertainty (k = 2) ranged from 11% to 17% and per needle uncertainty (k = 2) ranged from 18% to 110% (mean 31%). One out of 40 plans and 5% of needles were outside k = 2 error detection threshold. Conclusions: IVD showed good agreement with predicted dose within measurement uncertainties, providing reassurance in the accuracy of dose delivery. Thresholds for real-time error detection should be calculated on an individual plan/needle basis

Symplectic n-level densities with restricted support

In this paper, we demonstrate that the alternative form, derived by us in an earlier paper, of the [Formula: see text]-level densities for eigenvalues of matrices from the classical compact group [Formula: see text] is far better suited for comparison with derivations of the [Formula: see text]-level densities of zeros in the family of Dirichlet [Formula: see text]-functions associated with real quadratic characters than the traditional determinantal random matrix formula. Previous authors have found ingenious proofs that the leading order term of the [Formula: see text]-level density of the zeros agrees with the determinantal random matrix result under certain conditions, but here we show that comparison is more straightforward if the more suitable form of the random matrix result is used. For the support of the test function in [Formula: see text] and in [Formula: see text] we compare with existing number theoretical results. For support in [Formula: see text] no rigorous number theoretical result is known for the [Formula: see text]-level densities, but we derive the densities here using random matrix theory in the hope that this may make the path to a rigorous number theoretical result clearer. </jats:p

Correlation functions, null polygonal Wilson loops, and local operators

We consider the ratio of the correlation function of n+1 local operators over the correlator of the first n of these operators in planar N=4 super-Yang-Mills theory, and consider the limit where the first n operators become pairwise null separated. By studying the problem in twistor space, we prove that this is equivalent to the correlator of a n-cusp null polygonal Wilson loop with the remaining operator in general position, normalized by the expectation value of the Wilson loop itself, as recently conjectured by Alday, Buchbinder and Tseytlin. Twistor methods also provide a BCFW-like recursion relation for such correlators. Finally, we study the natural extension where n operators become pairwise null separated with k operators in general position. As an example, we perform an analysis of the resulting correlator for k=2 and discuss some of the difficulties associated to fixing the correlator completely in the strong coupling regime.Comment: 34 pages, 6 figures. v2: typos corrected and references added; v3: published versio

Young infants' visual fixation patterns in addition and subtraction tasks support an object tracking account.

This is the final version of the article. Available from Elsevier via the DOI in this record.Investigating infants' numerical ability is crucial to identifying the developmental origins of numeracy. Wynn (1992) claimed that 5-month-old infants understand addition and subtraction as indicated by longer looking at outcomes that violate numerical operations (i.e., 1+1=1 and 2-1=2). However, Wynn's claim was contentious, with others suggesting that her results might reflect a familiarity preference for the initial array or that they could be explained in terms of object tracking. To cast light on this controversy, Wynn's conditions were replicated with conventional looking time supplemented with eye-tracker data. In the incorrect outcome of 2 in a subtraction event (2-1=2), infants looked selectively at the incorrectly present object, a finding that is not predicted by an initial array preference account or a symbolic numerical account but that is consistent with a perceptual object tracking account. It appears that young infants can track at least one object over occlusion, and this may form the precursor of numerical ability.This research was funded by a grant from the Nuffield Foundation (SGS/32130) to the first author, a grant from the Economic and Social Research Council (RES-000-22-1113 and ES/K000934/1) to the first author, and grants from the National Institutes of Health (HD-48733 and HD-40432) to the last author. We thank the infants and parents for contributing to the research

Myocarditis related to Campylobacter jejuni infection: A case report

BACKGROUND: Myocarditis can develop as a complication of various infections and is most commonly linked to enterovirus infections. Myocarditis is rarely associated with bacterial infections; salmonellosis and shigellosis have been the most frequently reported bacterial cause. We report a case of myocarditis related to Campylobacter jejuni enteritis. CASE PRESENTATION: A 30-year-old previously healthy man presented with a history of prolonged chest pain radiating to the jaw and the left arm. Five days prior to the onset of chest pain, he developed bloody diarrhea, fever and chills. Creatine kinase (CK) and CK-MB were elevated to 289 U/L and 28.7 μg/L. Troponin I was 30.2 μg/L. The electrocardiogram (ECG) showed T wave inversion in the lateral and inferior leads. The chest pain resolved within 24 hours of admission. The patient had a completely normal ECG stress test. The patient was initiated on ciprofloxacin 500 mg po bid when Campylobacter jejuni was isolated from the stool. Diarrhea resolved within 48 hours of initiation of ciprofloxacin. The diagnosis of Campylobacter enteritis and related myocarditis was made based on the clinical and laboratory results and the patient was discharged from the hospital in stable condition. CONCLUSION: Myocarditis can be a rare but severe complication of infectious disease and should be considered as a diagnosis in patients presenting with chest pain and elevated cardiac enzymes in the absence of underlying coronary disease. It can lead to cardiomyopathy and congestive heart failure. There are only a few reported cases of myocarditis associated with Campylobacter infection

An assessment of road-verge grass as a feedstock for farm-fed anaerobic digestion plants

Cuttings from road-verge grass could provide biomass for energy generation, but currently this potential is not exploited. This research assessed the technical, practical and financial feasibility of using grass harvested from road verges as a feedstock in farm-fed anaerobic digestion (AD) plants. The methane potential (191 mL CH4 gDM−1) and digestion characteristics of verge grass were similar to those of current farm feedstocks; indicating suitability for AD. Ensiling had no significant impact on the biomethane generated. Testing co-digestions of verge grass with current farm feedstocks showed enhanced methane yields, suggesting that verge grass could be a valuable addition to AD feedstock mixes. In a case study of the UK county of Lincolnshire, potential volumes and locations of verge grass biomass were estimated, with capacities and locations of existing AD plants, to assess the potential to supply practical grass volumes. Grass harvesting costs were modelled and compared with other feedstock costs. Finally, the attitudes of AD operators to using verge grass were investigated to understand whether a market for verge grass exists. In a small survey all operators were willing to use it as a feedstock and most were prepared to pay over the estimated harvesting cost. If verge grass was legally recognised as a waste product it could be attractive to AD operators especially where financial incentives to use waste feedstocks are in place. In rural areas, verge grass could be harvested and co-digested by existing farm-fed AD plants, potentially reducing the cost of road verge maintenance and increasing biodiversity

Prenatal hypoxia induces increased cardiac contractility on a background of decreased capillary density.

Background: Chronic hypoxia in utero (CHU) is one of the most common insults to fetal development and may be associated with poor cardiac recovery from ischaemia-reperfusion injury,yet the effects on normal cardiac mechanical performance are poorly understood. Methods: Pregnant female wistar rats were exposed to hypoxia (12% oxygen, balance nitrogen)for days 10–20 of pregnancy. Pups were born into normal room air and weaned normally. At 10 weeks of age, hearts were excised under anaesthesia and underwent retrograde 'Langendorff' perfusion. Mechanical performance was measured at constant filling pressure (100 cm H2O) with intraventricular balloon. Left ventricular free wall was dissected away and capillary density estimated following alkaline phosphatase staining. Expression of SERCA2a and Nitric Oxide Synthases (NOS) proteins were estimated by immunoblotting. Results: CHU significantly increased body mass (P < 0.001) compared with age-matched control rats but was without effect on relative cardiac mass. For incremental increases in left ventricular balloon volume, diastolic pressure was preserved. However, systolic pressure was significantly greater following CHU for balloon volume = 50 μl (P < 0.01) and up to 200 μl (P < 0.05). For higher balloon volumes systolic pressure was not significantly different from control. Developed pressures were correspondingly increased relative to controls for balloon volumes up to 250 μl (P < 0.05).Left ventricular free wall capillary density was significantly decreased in both epicardium (18%; P <0.05) and endocardium (11%; P < 0.05) despite preserved coronary flow. Western blot analysis revealed no change to the expression of SERCA2a or nNOS but immuno-detectable eNOS protein was significantly decreased (P < 0.001) in cardiac tissue following chronic hypoxia in utero. Conclusion: These data offer potential mechanisms for poor recovery following ischaemia, including decreased coronary flow reserve and impaired angiogenesis with subsequent detrimental effects of post-natal cardiac performance

The actions of methotrexate on endothelial cells are dependent on the shear stress-induced regulation of one carbon metabolism

Objectives: The disease-modifying anti-rheumatic drug methotrexate (MTX) is recognized to reduce cardiovascular risk in patients with systemic inflammatory diseases. However, the molecular basis for these cardioprotective effects remains incompletely understood. This study evaluated the actions of low-dose MTX on the vascular endothelium. Methods: Human endothelial cells (EC) were studied under in vitro conditions relevant to inflammatory arthritis. These included culture in a pro-inflammatory microenvironment and exposure to fluid shear stress (FSS) using a parallel plate model. Respectively treated cells were analyzed by RNA sequencing and quantitative real-time PCR for gene expression, by immunoblotting for protein expression, by phosphokinase activity arrays, by flow cytometry for cell cycle analyses and by mass spectrometry to assess folate metabolite levels. Results: In static conditions, MTX was efficiently taken up by EC and caused cell cycle arrest concurrent with modulation of cell signaling pathways. These responses were reversed by folinic acid (FA), suggesting that OCM is a predominant target of MTX. Under FSS, MTX did not affect cell proliferation or pro-inflammatory gene expression. Exposure to FSS downregulated endothelial one carbon metabolism (OCM) as evidenced by decreased expression of key OCM genes and metabolites. Conclusion: We found that FSS significantly downregulated OCM and thereby rendered EC less susceptible to the effects of MTX treatment. The impact of shear stress on OCM suggested that MTX does not directly modulate endothelial function. The cardioprotective actions of MTX likely reflect direct actions on inflammatory cells and indirect benefit on the vascular endothelium

Collapse of superconductivity in a hybrid tin-graphene Josephson junction array

When a Josephson junction array is built with hybrid superconductor/metal/superconductor junctions, a quantum phase transition from a superconducting to a two-dimensional (2D) metallic ground state is predicted to happen upon increasing the junction normal state resistance. Owing to its surface-exposed 2D electron gas and its gate-tunable charge carrier density, graphene coupled to superconductors is the ideal platform to study the above-mentioned transition between ground states. Here we show that decorating graphene with a sparse and regular array of superconducting nanodisks enables to continuously gate-tune the quantum superconductor-to-metal transition of the Josephson junction array into a zero-temperature metallic state. The suppression of proximity-induced superconductivity is a direct consequence of the emergence of quantum fluctuations of the superconducting phase of the disks. Under perpendicular magnetic field, the competition between quantum fluctuations and disorder is responsible for the resilience at the lowest temperatures of a superconducting glassy state that persists above the upper critical field. Our results provide the entire phase diagram of the disorder and magnetic field-tuned transition and unveil the fundamental impact of quantum phase fluctuations in 2D superconducting systems.Comment: 25 pages, 6 figure

Sexual dimorphism in trait variability and its eco-evolutionary and statistical implications

Biomedical and clinical sciences are experiencing a renewed interest in the fact that males and females differ in many anatomic, physiological, and behavioural traits. Sex differences in trait variability, however, are yet to receive similar recognition. In medical science, mammalian females are assumed to have higher trait variability due to estrous cycles (the ‘estrus-mediated variability hypothesis’); historically in biomedical research, females have been excluded for this reason. Contrastingly, evolutionary theory and associated data support the ‘greater male variability hypothesis’. Here, we test these competing hypotheses in 218 traits measured in >26,900 mice, using meta-analysis methods. Neither hypothesis could universally explain patterns in trait variability. Sex bias in variability was trait-dependent. While greater male variability was found in morphological traits, females were much more variable in immunological traits. Sex-specific variability has eco-evolutionary ramifications, including sex-dependent responses to climate change, as well as statistical implications including power analysis considering sex difference in variance