A morphological study of the shape of the corpus callosum in normal, schizophrenic and bipolar patients

Abnormalities in the morphology of the corpus callosum have been found to be involved in cognitive impairments or abnormal behaviour in patients with mental disorders such as schizophrenia and bipolar disorder. The present study investigated morphological shape differences of the corpus callosum in a large cohort of 223 participants between normal, schizophrenic and bipolar patients on MRI scans, CT scans and cadaver samples. Healthy samples were compared to a mental disorder population sample to determine morphological shapes variations associated with schizophrenia and bipolar disorder. Landmark-based methodology was used to contour the corpus callosum shape that served as standard positions to allow for radial and thickness partitioning in order to determine shape variations within the specific localised anatomical sections of the corpus callosum. Shape analysis was performed using Ordinary Procrustes averaging and superimposing landmarks to define an average landmark position for the specific regions of the corpus callosum. No significant global shape differences were found between the different mental disorders. Schizophrenia and bipolar shapes differed mostly in the genu-rostrum, posterior body, isthmus and splenium. Sample group comparisons yielded significant differences between all groups and global measurement parameters and in various sub-regions. The findings of the present study suggest that the corpus callosum in schizophrenia and bipolar differs significantly compared to healthy controls, specifically in the anterior body and isthmus for schizophrenia and only in the isthmus for bipolar disorder. Shape changes in these regions may possibly, in part, be responsible for the symptoms and cognitive impairments observed in schizophrenia and bipolar disorder.http://wileyonlinelibrary.com/journal/joahj2023AnatomyPhysiolog

miR-181a is a novel player in the STAT3-mediated survival network of TCRαβ+ CD8+ T large granular lymphocyte leukemia

T-LGL cells arise as a consequence of chronic antigenic stimulation and inflammation and thrive because of constitutive activation of the STAT3 and ERK pathway. Notably, in 40% of patients, constitutive STAT3 activation is due to STAT3 activating mutations, whereas in 60% this is unknown. As miRNAs are amongst the most potent regulators in health and disease, we hypothesized that aberrant miRNA expression could contribute to dysregulation of these pathways. miRNA sequencing in T-LGL leukemia cases and aged-matched healthy control TEMRA cells revealed overexpression of miR-181a. Furthermore, geneset enrichment analysis (GSEA) of downregulated targets of miR-181a implicated involvement in regulating STAT3 and ERK1/2 pathways. Flow cytometric analyses showed increased SOCS3+ and DUSP6+ T-LGL cells upon miR-181a inhibition. In addition, miR-181a-transfected human CD8+ T cells showed increased basal STAT3 and ERK1/2 phosphorylation. By using TL1, a human T-LGL cell line, we could show that miR-181a is an actor in T-LGL leukemia, driving STAT3 activation by SOCS3 inhibition and ERK1/2 phosphorylation by DUSP6 inhibition and verified this mechanism in an independent cell line. In addition, miR-181a inhibition resulted in a higher sensitivity to FAS-mediated apoptosis. Collectively, our data show that miR-181a could be the missing link to explain why STAT3-unmutated patients show hyperactive STAT3

Investigating High-Energy Proton-Induced Reactions on Spherical Nuclei: Implications for the Pre-Equilibrium Exciton Model

A number of accelerator-based isotope production facilities utilize 100- to 200-MeV proton beams due to the high production rates enabled by high-intensity beam capabilities and the greater diversity of isotope production brought on by the long range of high-energy protons. However, nuclear reaction modeling at these energies can be challenging because of the interplay between different reaction modes and a lack of existing guiding cross section data. A Tri-lab collaboration has been formed among the Lawrence Berkeley, Los Alamos, and Brookhaven National Laboratories to address these complexities by characterizing charged-particle nuclear reactions relevant to the production of established and novel radioisotopes. In the inaugural collaboration experiments, stacked-targets of niobium foils were irradiated at the Brookhaven Linac Isotope Producer (E$_p$=200 MeV) and the Los Alamos Isotope Production Facility (E$_p$=100 MeV) to measure $^{93}$Nb(p,x) cross sections between 50 and 200 MeV. The measured cross-section results were compared with literature data as well as the default calculations of the nuclear model codes TALYS, CoH, EMPIRE, and ALICE. We developed a standardized procedure that determines the reaction model parameters that best reproduce the most prominent reaction channels in a physically justifiable manner. The primary focus of the procedure was to determine the best parametrization for the pre-equilibrium two-component exciton model. This modeling study revealed a trend toward a relative decrease for internal transition rates at intermediate proton energies (E$_p$=20-60 MeV) in the current exciton model as compared to the default values. The results of this work are instrumental for the planning, execution, and analysis essential to isotope production.Comment: 37 pages, 62 figures. Revised version, published in Physical Review

Quantitative Microbial Risk Assessment of Contracting COVID-19 Derived from Measured and Simulated Aerosol Particle Transmission in Aircraft Cabins

BACKGROUND: SARS-CoV-2 can be effectively transmitted between individuals located in close proximity to each other for extended durations. Aircraft provide such conditions. Although high attack rates during flights were reported, little was known about the risk levels of aerosol transmission of SARS-CoV-2 in aircraft cabins. OBJECTIVES: The major objective was to estimate the risk of contracting COVID-19 from transmission of aerosol particles in aircraft cabins. METHODS: In two single-aisle and one twin-aisle aircraft, dispersion of generated aerosol particles over a seven-row economy class cabin section was measured under cruise and taxi conditions and simulated with a computational fluid dynamic model under cruise conditions. Using the aerosol particle dispersion data, a quantitative microbial risk assessment was conducted for scenarios with an asymptomatic infectious person expelling aerosol particles by breathing and speaking. Effects of flight conditions were evaluated using generalized additive mixed models. RESULTS: Aerosol particle concentration decreased with increasing distance from the infectious person, and this decrease varied with direction. On a typical flight with an average shedder, estimated mean risk of contracting COVID-19 ranged from 1:3 × 10−3 to 9:0 × 10−2. Risk increased to 7:7 × 10−2 with a super shedder (<3% of cases) on a long flight. Risks increased with increasing flight duration: 2–23 cruise flights of typical duration and 2–10 flights of longer duration resulted in at least 1 case of COVID-19 due to onboard aerosol transmission by one average shedder, and in the case of one super shedder, at least 1 case in 1–3 flights of typical duration cruise and 1 flight of longer duration. DISCUSSION: Our findings indicate that the risk of contracting COVID-19 by aerosol transmission in an aircraft cabin is low, but it will not be zero. Testing before boarding may help reduce the chance of a (super)shedder boarding an aircraft and mask use further reduces aerosol transmission in the aircraft cabin

LEAK study:design of a nationwide randomised controlled trial to find the best way to treat wound leakage after primary hip and knee arthroplasty

INTRODUCTION: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are highly successful treatment modalities for advanced osteoarthritis. However, prolonged wound leakage after arthroplasty is linked to prosthetic joint infection (PJI), which is a potentially devastating complication. On the one hand, wound leakage is reported as a risk factor for PJI with a leaking wound acting as a porte d'entrée for micro-organisms. On the other hand, prolonged wound leakage can be a symptom of PJI. Literature addressing prolonged wound leakage is scarce, contradictory and of poor methodological quality. Hence, treatment of prolonged wound leakage varies considerably with both non-surgical and surgical treatment modalities. There is a definite need for evidence concerning the best way to treat prolonged wound leakage after joint arthroplasty. METHODS AND ANALYSIS: A prospective nationwide randomised controlled trial will be conducted in 35 hospitals in the Netherlands. The goal is to include 388 patients with persistent wound leakage 9-10 days after THA or TKA. These patients will be randomly allocated to non-surgical treatment (pressure bandages, (bed) rest and wound care) or surgical treatment (debridement, antibiotics and implant retention (DAIR)). DAIR will also be performed on all non-surgically treated patients with persistent wound leakage at day 16-17 after index surgery, regardless of amount of wound leakage, other clinical parameters or C reactive protein. Clinical data are entered into a web-based database. Patients are asked to fill in questionnaires about disease-specific outcomes, quality of life and cost effectiveness at 3, 6 and 12 months after surgery. Primary outcome is the number of revision surgeries due to infection within a year of arthroplasty. ETHICS AND DISSEMINATION: The Review Board of each participating hospital has approved the local feasibility. The results will be published in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NTR5960;Pre-results

The production of 139Pr and 139Ce in proton-induced reactions

Thesis (MSc (Chemistry and Polymer Science))--University of Stellenbosch, 2007.Excitation functions and production rates are presented for various Ce and Pr radionuclides formed in the bombardment of 141Pr, natLa and natCe with protons. Extensive measure- ments were performed for 141Pr + p up to 100 MeV and for natLa + p up to 20 MeV. The possibility is investigated to utilize tandem targetry for the production of no-carrier-added 139Ce of high radionuclidic purity, having a Pr target in the higher energy slot followed by a La target in a lower energy slot. 141Pr(p,3n)139mNd!139Pr is investigated as an al- ternative to the direct production route 140Ce(p,2n)139Pr for producing no-carrier-added 139Pr of high radionuclidic purity. The advantages and disadvantages of both production routes are discussed. The simultaneous production of 139Pr and 140Nd using Pr as target is also investigated. Experimental thick-target production rates are presented for Pr ra- dionuclides formed in the bombardment of natCe with protons at incident energies of 20, 26 and 32 MeV. All the experimental excitation functions obtained in this work are compared with theoretical predictions by means of the geometry-dependent hybrid (GDH) model as implemented in the code ALICE-IPPE. The results of this work are also compared with previous literature experimental data, if available

Production of radionuclides with medium energy protons with the emphasis on targetry

Thesis (PhD)--Stellenbosch University, 2014.ENGLISH ABSTRACT: The facilities for radionuclide production at iThemba LABS have undergone a number of significant upgrades over the last decade in order to increase the production capacity and to diversify the product portfolio. Central to this effort is a new vertical beam target station (VBTS) and its associated targetry, designed and built to operate at higher proton beam intensities for the large-scale production of relatively long-lived, high-value radionuclides such as 22Na, 68Ge and 82Sr. Along with the VBTS, an existing smaller horizontal beam target station was adapted to accommodate targetry for 18F production, mainly to supply 18F-FDG for use in positron emission tomography (PET). The production capacity was further enhanced by means of a beam splitter to enable bombardments in two target stations simultaneously. This required new developments on several systems, e.g. beam diagnostics, control, interlocking and cooling. This project brings together a number of different aspects of the upgraded facilities as well as the associated research and development that enable the production of radionuclides in the medium energy region, up to approximately 70 MeV. Investigations were performed on the cooling of the interfacial windows between the cyclotron vacuum and the targets as well as the direct cooling of the targets themselves during intense proton bombardments. For this purpose, empirical as well as computational fluid dynamics (CFD) calculations were performed. In addition, the local radiation shield of the VBTS as well as the beam transport in some of the targetry was investigated by means of Monte Carlo radiation transport calculations. Excitation functions for the production of various radionuclides in the 66 MeV proton bombardment of 192Os, 159Tb, natGd, 155Gd, 152Gd, 93Nb, natZr and 89Y were measured and compared with theoretical predictions by means of statistical nuclear model calculations as well as the TENDL-2012 library. In particular, the production of 186Re, selected radioterbiums (149;152;155Tb) and radiozirconiums (88;89Zr) is of interest in existing and emerging diagnostic and therapeutic applications in nuclear medicine. A study on 28Mg production in the proton bombardment of natCl using stacked chloride targets was also performed at 200 MeV. This radionuclide is of interest as 28Mg is the only practical radiotracer of Mg. Finally, new targetry for the production of 18F was developed, modelled and optimized for the non-standard degraded beam employed in this particular case.AFRIKAANSE OPSOMMING: Die fasiliteite vir die produksie van radionukliede by iThemba LABS is gedurende die afgelope dekade aansienlik opgegradeer om die produksiekapasiteit te verhoog en om die portfolio van produkte te diversifiseer. Sentraal tot hierdie poging is ’n vertikale-bundel skyfstasie (VBTS) wat gebou is om skywe met hoër intensiteit protonbundels te bombardeer ten einde relatief langlewende, hoë-waarde radionukliede op grootmaat te produseer, insluitende 22Na, 68Ge en 82Sr. Terselfdetyd is ’n bestaande, kleiner horisontale-bundel skyfstasie aangepas om skywe vir die produksie van 18F te huisves, meestal om 18FFDG vir positronemissietomografie (PET) te lewer. Die produksiekapasiteit is verder verhoog d.m.v. ’n bundeldeler sodat bundel gelyktyding aan twee skyfstasies gelewer kan word. Dit het ontwikkelingswerk vereis aan verskeie stelsels, insluitende diagnostiek, beheer, vergrendeling en verkoeling. Hierdie projek bring verskeie aspekte bymekaar t.o.v. die opgegradeerde produksiefasiliteite sowel as die geassosieerde navorsing en ontwikkeling benodig vir radionukliedproduksie in die middelenergiegebied tot ongeveer 70 MeV. Die verkoeling van die foelievensters tussen die vakuum van die siklotron en die skyfgerei is ondersoek sowel as die direkte verkoeling van skywe onder intense protonbombardement. Hierdie studie sluit beide empiriese sowel as numeriese vloeidinamika berekeninge in. Verder is die afskerming van die VBTS asook die bundeltransport in verskeie skywe ondersoek m.b.v. Monte Carlo stralingstransport berekeninge. Opwekkrommes vir die produksie van verskeie radionukliede met protongeïnduseerde reaksies tot en met 66 MeV op 192Os, 159Tb, natGd, 155Gd, 152Gd, 93Nb, natZr en 89Y is gemeet en vergelyk met statistiese kernmodel berekeninge sowel as die TENDL-2012 biblioteek. Die produksie van 186Re, verskeie radioterbiums (149;152;155Tb) en radiozirkoniums (88;89Zr) is van spesifieke belang vir bestaande en toekomstige diagnostiese en terapeutiese toepassings in die kerngeneeskunde. ’n Studie op die produksie van 28Mg in die bombardement van natCl met 200 MeV protone is ook onderneem. In hierdie ondersoek is ’n stapel chloriedskywe gebruik. Die 28Mg is van belang omdat dit die enigste Mg radioisotoop is wat geskik is as ’n radiospoorder van dié element. Laastens is nuwe skyfgerei vir die produksie van 18F ontwikkel, gemodelleer en geoptimiseer vir die nie-standaard afgeremde bundel wat benut word in hierdie geval

Multi-jet gas cooling of in-beam foils or specimens: CFD predictions of the convective heat-transfer coefficient

An experiment was designed to investigate the possible enhancement of the convective heat-transfer coefficient by utilizing multiple, parallel jets in the cooling of a small heated surface, such as typically induced by an accelerated ion beam on a thin foil or specimen. The hot spot was provided using a small electrically heated plate. It was found that heat-transfer calculations by means of simple empirical methods based on dimensional analysis are not useful in this case and that advanced computational fluid dynamics (CFD) mod-elling is essential to interpret the results. It is shown that enhanced convective cooling can indeed be obtained with a multi-jet configuration as compared to a single-jet configuration but only under very selective conditions. An improperly designed multi-jet configuration can also provide significantly reduced cooling relative to the single-jet case and the estimation of the behavior of any particular jet geometry is eminently non-intuitive. CFD provides acceptable quantitative results and seem to be the only tool available to gain an understanding of these complex flows where simple models and “rules of thumb” cannot be relied upon. – LA-UR-18-2945