Split-bolus single-phase versus single-bolus split-phase CT acquisition protocols for staging in patients with testicular cancer: A retrospective study.

INTRODUCTION: Computed tomography (CT) imaging has become indispensable in the management of medical oncology patients. Risks associated with high cumulative effective dose (CED) are relevant in testicular cancer patients. Split-bolus protocols, whereby the contrast medium injection is divided into two, followed by combining the required phase images in a single scan acquisition has been shown to provide images of comparable image quality and less radiation dose compared to single-bolus split-phase CT for various indications. We retrospectively evaluated the performance of split-bolus and single-bolus protocols in patients having follow-up CT imaging for testicular cancer surveillance. METHODS: 45 patients with testicular cancer undergoing surveillance CT imaging of the thorax, abdomen, and pelvis who underwent split-bolus and single-bolus protocols were included. Quantitative image quality analysis was conducted by placing region of interests in pre-defined anatomical sub-structures within the abdominal cavity. The signal-to-noise ratio (SNR) and radiation dose in the form of dose length product (DLP) and effective dose (ED) were recorded. RESULTS: The DLP and ED for the single-bolus, split-phase acquisition was 506 ± 89 mGy cm and 7.59 ± 1.3 mSv, respectively. For the split-bolus, single-phase acquisition, 397 ± 94 mGy∗cm and 5.95 ± 1.4 mSv, respectively (p < 0.000). This represented a 21.5 % reduction in radiation dose exposure. The SNR for liver, muscle and fat for the single-bolus were 7.4, 4.7 and 8, respectively, compared to 5.5, 3.8 and 7.4 in the split-bolus protocol (p < 0.001). CONCLUSION: In a testicular cancer patient cohort undergoing surveillance CT imaging, utilization of a split-bolus single-phase acquisition CT protocol enabled a significant reduction in radiation dose whilst maintaining subjective diagnostic acceptability. IMPLICATIONS FOR PRACTICE: Use of split-bolus, single-phase acquisition has the potential to reduce CED in surveillance of testicular cancer patients.

Determination of the Terbium-152 half-life from mass-separated samples from CERN-ISOLDE and assessment of the radionuclide purity.

Terbium-152 is one of four terbium radioisotopes that together form a potential theranostic toolbox for the personalised treatment of tumours. As 152 Tb decay by positron emission it can be utilised for diagnostics by positron emission tomography. For use in radiopharmaceuticals and for activity measurements by an activity calibrator a high radionuclide purity of the material and an accurate and precise knowledge of the half-life is required. Mass-separation and radiochemical purification provide a production route of high purity 152Tb. In the current work, two mass-separated samples from the CERN-ISOLDE facility have been assayed at the National Physical Laboratory to investigate the radionuclide purity. These samples have been used to perform four measurements of the half-life by three independent techniques: high-purity germanium gamma-ray spectrometry, ionisation chamber measurements and liquid scintillation counting. From the four measurement campaigns a half-life of 17.8784(95) h has been determined. The reported half-life shows a significant difference to the currently evaluated half-life (ζ-score = 3.77), with a relative difference of 2.2 % and an order of magnitude improvement in the precision. This work also shows that under controlled conditions the combination of mass-separation and radiochemical separation can provide high-purity 152Tb.

A plastic scintillator and HPGe ß-γ coincidence detection system.

A network of specialist laboratories support the International Monitoring System (IMS) of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) with re-measurements of radionuclide samples, including xenon gas. The measurement of four xenon fission product radionuclides (133Xe, 135Xe, 131mXe and 133mXe) can be used to detect an underground nuclear explosion. Laboratories use a range of techniques to measure the radionuclides, including beta-gamma (ß-γ) coincidence spectrometry. These highly-sensitive measurements are capable of detecting concentrations of down to 500 atoms of 133Xe in a few cm3 of xenon. In some detector systems, detection of the metastable isomers (131mXe and 133mXe) can be more challenging due to interferences between the signatures of different radionuclides. Recent work has shown that using high-purity Germanium (HPGe) high-resolution gamma detectors, these interferences can be reduced, lowering the dependence of the detection limits on radionuclide sample isotopic composition. One downside of these detectors is the reduction in detection efficiency, which impacts the overall detection sensitivity; so assessing different detector systems is a priority for radionuclide laboratories. This work presents a coincidence detector system comprising of a plastic scintillator gas cell and a large-crystal high-purity germanium detector. The energy resolution, coincidence detection efficiency, MDA and interference factors are determined from measurements of synthetic radioxenon gas samples.

Half-life determination of 155Tb from mass-separated samples produced at CERN-MEDICIS.

Terbium-155 has been identified for its potential for single-photon emission computed tomography (SPECT) in nuclear medicine. For activity measurements, an accurate and precise half-life of this radionuclide is required. However, the currently evaluated half-life of 5.32(6) d with a relative standard uncertainty of 1.1% determines the precision possible. Limited literature for the half-life measurements of this radionuclide is available and all reported investigations are prior to 1970. Further measurements are therefore needed to confirm the accuracy and improve the precision of the half-life for its use in the clinical setting. Two samples produced and mass separated at the CERN-MEDICIS facility have been measured at the National Physical Laboratory by two independent techniques: liquid scintillation counting and high-purity germanium gamma-ray spectrometry. A half-life of 5.2346(36) d has been determined from the weighted mean of the half-lives determined by the two techniques. The half-life reported in this work has shown a relative difference of 1.6% to the currently evaluated half-life and has vastly improved the precision.

Head and Neck Merkel Cell Carcinoma: A 12-Year Single Institutional Experience.

Background: Merkel cell carcinoma (MCC) is an aggressive malignancy of presumed neuroendocrine origin. Most case series of MCC are limited by low case numbers and are not specific to head and neck tumours. The purpose of this study was to provide a focused review of head and neck MCC diagnosis and management in a single Irish institution. Methods: Patient's demographics, tumour characteristics, pathological diagnosis, surgical treatment, adjuvant treatment, subsequent management and clinical course were collected. Estimates of progression-free MCC survival rates were calculated by the Kaplan-Meier statistical model. A Pearson product-moment correlation coefficient examined the association between surgical margins and disease-free follow-up. Results: In total, 11 patients were treated for head and neck MCC with a mean age of 79.6 years (range = 69-91 years). The mean average follow-up duration of patients was 18.3 months. Of the cohort, 18% (n=2) had a sentinel node biopsy (SLNB). A selective neck dissection was subsequently performed in 18% (n=2). In total, 72% (n=8) of patients received adjuvant radiotherapy. Median disease-specific survival was 15 months for the SLNB group and 17 months for the non-SLNB group, not statistically significant (p=0.23). There was no significant association between surgical margins and disease-free follow (p=0.65). Conclusions: Our case series adds to a limited body of evidence of head and neck MCC. Surgery remains the treatment priority in localized disease, with an increasing role of SLNB for accurate prognostication and staging. Early management of stage I disease results in moderate long-term disease-free survivability.

Superresolution microscopy reveals actomyosin dynamics in medioapical arrays.

Arrays of actin filaments (F-actin) near the apical surface of epithelial cells (medioapical arrays) contribute to apical constriction and morphogenesis throughout phylogeny. Here, superresolution approaches (grazing incidence structured illumination, GI-SIM, and lattice light sheet, LLSM) microscopy resolve individual, fluorescently labeled F-actin and bipolar myosin filaments that drive amnioserosa cell shape changes during dorsal closure in Drosophila. In expanded cells, F-actin and myosin form loose, apically domed meshworks at the plasma membrane. The arrays condense as cells contract, drawing the domes into the plane of the junctional belts. As condensation continues, individual filaments are no longer uniformly apparent. As cells expand, arrays of actomyosin are again resolved-some F-actin turnover likely occurs, but a large fraction of existing filaments rearrange. In morphologically isotropic cells, actin filaments are randomly oriented and during contraction are drawn together but remain essentially randomly oriented. In anisotropic cells, largely parallel actin filaments are drawn closer to one another. Our images offer unparalleled resolution of F-actin in embryonic tissue, show that medioapical arrays are tightly apposed to the plasma membrane and are continuous with meshworks of lamellar F-actin. Medioapical arrays thereby constitute modified cell cortex. In concert with other tagged array components, superresolution imaging of live specimens will offer new understanding of cortical architecture and function.

Determination of the 161Tb half-life.

There is significant interest in the use of terbium radioisotopes for applications in cancer therapy and diagnosis. Of these, 161Tb, as a medium energy beta-emitter, is being investigated as a potential alternative to 177Lu. The relatively high proportion of conversion electron and Auger electron emissions per decay make 161Tb an attractive targeted therapeutic. As a product of nuclear fission, 161Tb is also of importance to nuclear forensics. The standard uncertainty of the current evaluated half-life of 6.89(2) d contributes significantly to the standard uncertainty of any decay corrected activity determination made. Furthermore, the accuracy of this evaluated half-life has been called into question by measurements reported in 2020 at the Institute of Radiation Physics (IRA), Switzerland, who reported a half-life of 6.953(2) d. In the current work, the half-life of the 161Tb ground state decay has been measured at three independent laboratories located in the United Kingdom and the United States of America for a total of six determinations using three independent measurement techniques; gamma-ray spectrometry, ionisation chamber measurement and liquid scintillation counting. The half-life determined for 161Tb of 6.9637(29) d confirms the observed 1% relative increase observed by IRA, though the reported half-lives in this work and at IRA are significantly different (ζ-score = 3.1).

A multi-functional microfluidic device compatible with widefield and light sheet microscopy.

We present a microfluidic device compatible with high resolution light sheet and super-resolution microscopy. The device is a 150 µm thick chamber with a transparent fluorinated ethylene propylene (FEP) cover that has a similar refractive index (1.34) to water (1.33), making it compatible with top-down imaging used in light sheet microscopy. We provide a detailed fabrication protocol and characterize the optical performance of the device. We demonstrate that the device supports long-term imaging of cell growth and differentiation as well as the rapid addition and removal of reagents while simultaneously maintaining sterile culture conditions by physically isolating the sample from the dipping lenses used for imaging. Finally, we demonstrate that the device can be used for super-resolution imaging using lattice light sheet structured illumination microscopy (LLS-SIM) and DNA PAINT. We anticipate that FEP-based microfluidics, as shown here, will be broadly useful to researchers using light sheet microscopy due to the ability to switch reagents, image weakly adherent cells, maintain sterility, and physically isolate the specimen from the optics of the instruments.

Competition between Allowed and First-Forbidden ß Decay: The Case of

The ß decay of ^{208}Hg into the one-proton hole, one neutron-particle _{81}^{208}Tl_{127} nucleus was investigated at CERN-ISOLDE. Shell-model calculations describe well the level scheme deduced, validating the proton-neutron interactions used, with implications for the whole of the N>126, Z<82 quadrant of neutron-rich nuclei. While both negative and positive parity states with spin 0 and 1 are expected within the Q_{ß} window, only three negative parity states are populated directly in the ß decay. The data provide a unique test of the competition between allowed Gamow-Teller and Fermi, and first-forbidden ß decays, essential for the understanding of the nucleosynthesis of heavy nuclei in the rapid neutron capture process. Furthermore, the observation of the parity changing 0^{+}→0^{-}ß decay where the daughter state is core excited is unique, and can provide information on mesonic corrections of effective operators.

Identifying Key Genetic Regions for Cell Sheet Morphogenesis on Chromosome 2L Using a Drosophila Deficiency Screen in Dorsal Closure.

Cell sheet morphogenesis is essential for metazoan development and homeostasis of animal form - it contributes to developmental milestones including gastrulation, neural tube closure, heart and palate formation and to tissue maintenance during wound healing. Dorsal closure, a well-characterized stage in Drosophila embryogenesis and a model for cell sheet morphogenesis, is a remarkably robust process during which coordination of conserved gene expression patterns and signaling cascades regulate the cellular shape changes and movements. New 'dorsal closure genes' continue to be discovered due to advances in imaging and genetics. Here, we extend our previous study of the right arm of the 2nd chromosome to the left arm of the 2nd chromosome using the Bloomington deficiency kit's set of large deletions, which collectively remove 98.9% of the genes on the left arm of chromosome two (2L) to identify 'dorsal closure deficiencies'. We successfully screened 87.2% of the genes and identified diverse dorsal closure defects in embryos homozygous for 49 deficiencies, 27 of which delete no known dorsal closure gene. These homozygous deficiencies cause defects in cell shape, canthus formation and tissue dynamics. Within these deficiencies, we have identified pimples, odd-skipped, paired, and sloppy-paired 1 as dorsal closure genes on 2L that affect lateral epidermal cells. We will continue to identify novel 'dorsal closure genes' with further analysis. These forward genetic screens are expected to identify new processes and pathways that contribute to closure and links between pathways and structures already known to coordinate various aspects of closure.

Population Data-Driven Formulation of a COVID-19 Therapeutic

This study is designed to utilize computer modeling of the US population through NHANES to reduce the need for preclinical formulation and toxicology studies of an Ebola anti-viral (BSN389) being repurposed for COVID-19, and to thereby speed the candidate therapeutic to the clinic.

Advances in the Direct Study of Carbon Burning in Massive Stars.

The ^{12}C+^{12}C fusion reaction plays a critical role in the evolution of massive stars and also strongly impacts various explosive astrophysical scenarios. The presence of resonances in this reaction at energies around and below the Coulomb barrier makes it impossible to carry out a simple extrapolation down to the Gamow window-the energy regime relevant to carbon burning in massive stars. The ^{12}C+^{12}C system forms a unique laboratory for challenging the contemporary picture of deep sub-barrier fusion (possible sub-barrier hindrance) and its interplay with nuclear structure (sub-barrier resonances). Here, we show that direct measurements of the ^{12}C+^{12}C fusion cross section may be made into the Gamow window using an advanced particle-gamma coincidence technique. The sensitivity of this technique effectively removes ambiguities in existing measurements made with gamma ray or charged-particle detection alone. The present cross-section data span over 8 orders of magnitude and support the fusion-hindrance model at deep sub-barrier energies.

The impact of high-energy tailing in high-purity germanium gamma-ray spectrometry on the activity determination of 224Ra using the 241.0 keV emission.

High-energy tailing is an often-overlooked component in high-purity germanium gamma-ray spectrometry when performing the non-linear least squares fit of a full-energy peak. This component comes from the incomplete restoration of the baseline prior to the next pulse being processed and therefore is an issue of increased count rates. In the current work, the impact of this oversight is shown through the dynamics and decay characteristics of 224Ra and its radioactive decay progeny. Multiple measurements of two samples, separated from the decay progeny and at differing activities, have been made. The results of full-energy peak fitting of the convoluted 238.6 keV and 241.0 keV full-energy peaks with and without the high energy tailing component are presented. Trends in the observed activity that approximate the ingrowth of 212Pb have been observed where no high-energy tailing component is used, with maximum relative differences of 2% and 5% determined.

A new adaptation for a secure surgical drain placement and a comparison with four common drain fixation methods.

INTRODUCTION: The importance of postoperative drain fixation cannot be overemphasised. There are numerous described techniques for drain fixation. However, to our knowledge, there is no evidence-based comparison between the various techniques of drain fixation used in postoperative management. We describe a new method and compare its reliability with four other commonly used methods. MATERIALS AND METHODS: Five methods were chosen for testing based on current trends in clinical practice: centurion sandal with plastic locking ties, centurion sandal or lattice method, centurion sandal with half-inch Steristrips®, double and multiple looped methods. We used an Instron 8872® tensiometer to apply a measured force to a secured drain. Each fixation method was tested ten times and all fixation methods were performed by the same experienced surgeon. We measured the average number of cycles before failure, the average displacement of the tube at failure and the time needed to apply each fixation method. RESULTS: The number of cycles completed before failure showed that the centurion sandal method, the centurion sandal with plastic ties and the centurion sandal method with Steristrips had the lowest failure rate. The amount of displacement was the least in the centurion sandal with plastic ties followed by the double-loop method and centurion sandal with Steristrips. There was little difference in the time taken to complete the fixation methods (range 21-33 seconds). DISCUSSION: We recommend the use of the centurion sandal with plastic locking ties, centurion sandal with Steristrips followed by the centurion sandal method alone as fixation techniques that are quick to perform, secure and reliable.

Visualizing Intracellular Organelle and Cytoskeletal Interactions at Nanoscale Resolution on Millisecond Timescales.

In eukaryotic cells, organelles and the cytoskeleton undergo highly dynamic yet organized interactions capable of orchestrating complex cellular functions. Visualizing these interactions requires noninvasive, long-duration imaging of the intracellular environment at high spatiotemporal resolution and low background. To achieve these normally opposing goals, we developed grazing incidence structured illumination microscopy (GI-SIM) that is capable of imaging dynamic events near the basal cell cortex at 97-nm resolution and 266 frames/s over thousands of time points. We employed multi-color GI-SIM to characterize the fast dynamic interactions of diverse organelles and the cytoskeleton, shedding new light on the complex behaviors of these structures. Precise measurements of microtubule growth or shrinkage events helped distinguish among models of microtubule dynamic instability. Analysis of endoplasmic reticulum (ER) interactions with other organelles or microtubules uncovered new ER remodeling mechanisms, such as hitchhiking of the ER on motile organelles. Finally, ER-mitochondria contact sites were found to promote both mitochondrial fission and fusion.

Selective sorption of uranium from aqueous solution by graphene oxide-modified materials.

The effect of competing ions on the sorption behaviour of uranium onto carboxyl-functionalised graphene oxide (COOH-GO) were studied in batch experiments in comparison to graphene oxide (GO) and graphite. The effect of increasing the abundance of select chemical functional groups, such as carboxyl groups, on the selectivity of U sorption was investigated. In the course of the study, COOH-GO demonstrated superior performance as a sorbent material for the selective removal of uranyl ions from aqueous solution with a distribution coefficient of 3.72 ± 0.19 × 103 mL g-1 in comparison to 3.97 ± 0.5 × 102 and 2.68 ± 0.2 × 102 mL g-1 for GO and graphite, respectively.

Identifying Genetic Players in Cell Sheet Morphogenesis Using a Drosophila Deficiency Screen for Genes on Chromosome 2R Involved in Dorsal Closure.

Cell sheet morphogenesis characterizes key developmental transitions and homeostasis, in vertebrates and throughout phylogeny, including gastrulation, neural tube formation and wound healing. Dorsal closure, a process during Drosophila embryogenesis, has emerged as a model for cell sheet morphogenesis. ∼140 genes are currently known to affect dorsal closure and new genes are identified each year. Many of these genes were identified in screens that resulted in arrested development. Dorsal closure is remarkably robust and many questions regarding the molecular mechanisms involved in this complex biological process remain. Thus, it is important to identify all genes that contribute to the kinematics and dynamics of closure. Here, we used a set of large deletions (deficiencies), which collectively remove 98.5% of the genes on the right arm of Drosophila melanogaster's 2nd chromosome to identify "dorsal closure deficiencies". Through two crosses, we unambiguously identified embryos homozygous for each deficiency and time-lapse imaged them for the duration of closure. Images were analyzed for defects in cell shapes and tissue movements. Embryos homozygous for 47 deficiencies have notable, diverse defects in closure, demonstrating that a number of discrete processes comprise closure and are susceptible to mutational disruption. Further analysis of these deficiencies will lead to the identification of at least 30 novel "dorsal closure genes". We expect that many of these novel genes will identify links to pathways and structures already known to coordinate various aspects of closure. We also expect to identify new processes and pathways that contribute to closure.

Investigation of γ-γ coincidence counting using the National Nuclear Array (NANA) as a primary standard.

The National Physical Laboratory has recently been in the process of commissioning a multi-detector γ ray array - the National Nuclear Array (NANA). In this study we have sought to exploit the NANA and the excellent timing characteristics of its intrinsic LaBr3(Ce) scintillation detectors for use as a primary standardisation system. For this initial investigation, the absolute standardisation of 60Co has been performed by the γ-γ coincidence technique using NANA and the result compared to the established 4π(LS)-γ Digital Coincidence Counting (DCC) system. The effect of the angular correlation of the stretched E2 transitions emitted from the 4+→2+→0 states of 60Ni on the activity determined by NANA was observed between the pairs of detectors. Corrections for these angular correlations were derived through Monte Carlo simulations. An activity per unit mass by NANA of 330.8 (10) kBqg-1 for the 60Co solution was determined. There was no significant statistical difference between the results of NANA and the 4π(LS)-γ DCC, with a relative difference of 0.04% observed. This study shows that NANA can be used as a primary standard.