Magnetic confinement of radiotherapy beam-dose profiles

We have used electron and photon beams from the 50 MV electron microtron at UM Hospital together with a large-bore 3.5T superconducting solenoid to demonstrate the magnetic confinement of HE electron and photon beam-dose profiles for typical radiotherapy beams. The HE electron beams in particular exhibit a large reduction in penumbra when entering a tissue-equivalent phantom and, in addition, confinement of the secondary electrons produced by the primary beam. Likewise photon beams show a similar confinement of the dose from secondary electrons. While the results resemble features predicted from Monte Carlo calculations, there are a number of anomalous details in the actual experimental data which serve to illustrate the problems associated with practical clinical implementations. However the data suggest that in certain cases HE electrons may provide a cost-effective alternate to proton or HI radiotherapy beams and, also, improve the dose profile for HE photon beams. © 2001 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87615/2/44_1.pd

The impact of perceived donor liver quality on post-transplant outcome.

BACKGROUND We analysed the impact of perceived liver donor quality on transplant recipient outcomes. METHODS this prospective cohort study included all deceased liver donors during 2008-2018 in the Swiss Transplant Cohort Study. Perceived low-quality liver donors were defined when refused for ≥5 top listed recipients or for all recipients in at least one centre before being transplanted. The effect of liver donor quality on relisting or recipient death at 1 week and 1 year after transplantation was analysed using Kaplan-Meier and Cox proportional hazard models. A 1:3 matching was also performed using a recipient score. RESULTS Of 973 liver donors, 187 (19.2%) had perceived poor-quality. Males, obesity, donation after circulatory death and alanine aminotransferase values were significantly associated with perceived poor-quality, with no significant effect of the perceived quality on re-listing or death within the first week and first year post-transplant [(aHR) = 1.45, 95% CI: (0.6, 3.5), P = 0.41 and aHR = 1.52 (95% CI 0.98-2.35), P = 0.06], adjusting by recipient age and gender, obesity, diabetes, prior liver transplantation and model for end-stage liver disease (MELD) score. At 1 year, prior liver transplantation and higher MELD score associated with higher risk of re-listing or death. CONCLUSION Comparable post-transplant outcomes with different perceived quality liver donors stresses the need to improve donor selection in liver transplantation

The Forum: Summer 2002

Summer 2002 journal of the Honors Program at the University of North Dakota. The issue includes stories, poems, essays and art by undergraduate students.https://commons.und.edu/und-books/1049/thumbnail.jp

NOTE: An apparatus for applying strong longitudinal magnetic fields to clinical photon and electron beams

Monte Carlo studies have recently renewed interest in the use of the effect of strong transverse and longitudinal magnetic fields to manipulate the dose characteristics of clinical photon and electron beams. A 3.5 T superconducting solenoidal magnet was used to evaluate the effect of a longitudinal field on both photon and electron beams. This note describes the apparatus and demonstrates some of the effects on the beam trajectory and dose distributions for measurements in a homogeneous phantom. The effects were studied using film in air and in phantoms which fit in the magnet bore. The magnetic field focused and collimated the electron beams. The converging, non-uniform field confined the beam and caused it to converge with increasing depth in the phantom. Due to the field's collecting and focusing effect, the beam flux density increased, leading to increased dose deposition near the magnetic axis, especially near the surface of the phantom. This study illustrates some benefits and challenges associated with the use of non-uniform longitudinal magnetic fields in conjunction with clinical electron and photon beams.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48970/2/m105n1.pd

Fluorescence-based high-throughput functional profiling of ligand-gated ion channels at the level of single cells

Ion channels are involved in many physiological processes and are attractive targets for therapeutic intervention. Their functional properties vary according to their subunit composition, which in turn varies in a developmental and tissue-specific manner and as a consequence of pathophysiological events. Understanding this diversity requires functional analysis of ion channel properties in large numbers of individual cells. Functional characterisation of ligand-gated channels involves quantitating agonist and drug dose-response relationships using electrophysiological or fluorescence-based techniques. Electrophysiology is limited by low throughput and high-throughput fluorescence-based functional evaluation generally does not enable the characterization of the functional properties of each individual cell. Here we describe a fluorescence-based assay that characterizes functional channel properties at single cell resolution in high throughput mode. It is based on progressive receptor activation and iterative fluorescence imaging and delivers >100 dose-responses in a single well of a 384-well plate, using α1-3 homomeric and αβ heteromeric glycine receptor (GlyR) chloride channels as a model system. We applied this assay with transiently transfected HEK293 cells co-expressing halide-sensitive yellow fluorescent protein and different GlyR subunit combinations. Glycine EC values of different GlyR isoforms were highly correlated with published electrophysiological data and confirm previously reported pharmacological profiles for the GlyR inhibitors, picrotoxin, strychnine and lindane. We show that inter and intra well variability is low and that clustering of functional phenotypes permits identification of drugs with subunit-specific pharmacological profiles. As this method dramatically improves the efficiency with which ion channel populations can be characterized in the context of cellular heterogeneity, it should facilitate systems-level analysis of ion channel properties in health and disease and the discovery of therapeutics to reverse pathological alterations

Amino Acid Residues Contributing to Function of the Heteromeric Insect Olfactory Receptor Complex

Olfactory receptors (Ors) convert chemical signals—the binding of odors and pheromones—to electrical signals through the depolarization of olfactory sensory neurons. Vertebrates Ors are G-protein-coupled receptors, stimulated by odors to produce intracellular second messengers that gate ion channels. Insect Ors are a heteromultimeric complex of unknown stoichiometry of two seven transmembrane domain proteins with no sequence similarity to and the opposite membrane topology of G-protein-coupled receptors. The functional insect Or comprises an odor- or pheromone-specific Or subunit and the Orco co-receptor, which is highly conserved in all insect species. The insect Or-Orco complex has been proposed to function as a novel type of ligand-gated nonselective cation channel possibly modulated by G-proteins. However, the Or-Orco proteins lack homology to any known family of ion channel and lack known functional domains. Therefore, the mechanisms by which odors activate the Or-Orco complex and how ions permeate this complex remain unknown. To begin to address the relationship between Or-Orco structure and function, we performed site-directed mutagenesis of all 83 conserved Glu, Asp, or Tyr residues in the silkmoth BmOr-1-Orco pheromone receptor complex and measured functional properties of mutant channels expressed in Xenopus oocytes. 13 of 83 mutations in BmOr-1 and BmOrco altered the reversal potential and rectification index of the BmOr-1-Orco complex. Three of the 13 amino acids (D299 and E356 in BmOr-1 and Y464 in BmOrco) altered both current-voltage relationships and K+ selectivity. We introduced the homologous Orco Y464 residue into Drosophila Orco in vivo, and observed variable effects on spontaneous and evoked action potentials in olfactory neurons that depended on the particular Or-Orco complex examined. Our results provide evidence that a subset of conserved Glu, Asp and Tyr residues in both subunits are essential for channel activity of the heteromeric insect Or-Orco complex

Physical activity decreases in patients on the liver transplant waiting list and influences postoperative outcome-a prospective cohort study.

BACKGROUND Physical deconditioning affects patients suffering from end-stage liver disease (ESLD). Liver transplantation (LT) is the only curative option for ESLD. Growing evidence suggests that pre-habilitation is beneficial in reducing post-surgical morbidity and mortality. We investigated physical activity (PA) in patients awaiting LT in a country with long waiting times. METHODS Prospective, single center, longitudinal study in Bern, Switzerland between June 2019 and February 2020 (halted due to SARS-CoV-2 pandemic), with follow-up data up to six months post-transplant. Patients were instructed to use a wrist tracker (FitBit) to monitor PA, which was assessed using mixed-effects generalized linear models. The study was approved by the local ethics committee (BASEC ID 2019-00606). RESULTS Thirty-five patients were included [71% male, median 59 years, body mass index (BMI) 28 kg/m2, lab Model End-Stage Liver Disease (MELD) 11], 17 (49%) pre-frail and 5 (14%) frail according to the Liver Frailty Index (LFI). Twenty-eight patients underwent transplantation with 0 ninety-day mortality and 15 (53.6%) composite adverse clinical outcome. Median daily steps were 4,661 [interquartile range (IQR), 1,685-8,609] and weekly moderate PA (MPA) was 41 min (IQR, 0-127 min). Longitudinal analysis showed that female patients and patients on nutritional support had an increase in MPA between weeks 20 and 40. A significant decrease was seen in MPA after week 40, whilst no significant association was seen with age, Child-Pugh Score, LFI or quality of life at time of inclusion. MPA was significantly associated with the occurrence of the composite clinical endpoint after week 30 of waiting time (odds ratio 0.882, P=0.026). World Health Organization (WHO)-recommended MPA was significantly associated with less adverse composite clinical outcomes (P<0.001). CONCLUSIONS In patients listed for LT, MPA decreased over time, showing a significant association with adverse outcome, specifically after week 30 on the waiting list. Our data support the implementation of routine pre-habilitation in patients awaiting LT