Thesis (M. Phil.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

Thesis (M.A.)--University of Calgary, 2005. / Includes bibliographical references (p. 110-117)

Section 1 of the Income Tax Act, 58 of 1962 (the Income Tax Act) and other related Revenue Acts empower the South African Revenue Service (SARS) to administer the Acts and to collect revenue for the government of the Republic of South Africa. Sometimes, in order to assess tax liability and collect revenue, the Commissioner and/or officials of SARS have to make certain representations and undertakings to taxpayers in general through interpretation notes, rulings, and other forms of communication. In certain circumstances, SARS is authorised to withdraw rulings made and at times already acted upon, often to the taxpayer’s detriment. This results in lack of clarity, uncertainty and inconsistency in the application of the law. In order to address this problem, an Advanced Tax Ruling System (ATRS) was introduced. In terms of the ATRS, the issuing of rulings is statutorily regulated and binding on both the taxpayer and SARS when certain conditions provided for in the Income Tax Act are met. The purpose of an ATRS is to promote clarity, consistency, and certainty in respect of the interpretation or application of the provisions of tax laws to which it applies. However, the Commissioner is not obliged to follow a policy or undertaking which is in violation of tax laws. Section 76N(3) provides that the Commissioner may withdraw or modify a binding private ruling, or a binding class ruling retrospectively, if the ruling was made in error; subject to sub paragraphs (a), (b) and (c) thereof. This creates uncertainty as opposed to the intention for which the ATRS was introduced. The critical question is, if the Commissioner timeously informed the taxpayer that he has decided not to honour the undertaking made in a valid binding private ruling, which is still in force to the detriment of the taxpayer, can the taxpayer raise a defence of substantive legitimate expectation? It is argued that the issuing of an ATR is an administrative action subject to judicial review, if, in the opinion of the concerned party, it will have an adverse effect. Further, in the event that the Commissioner informs the taxpayer timeously of the intention to withdraw a valid binding private ruling, which the taxpayer has acted upon to their detriment, can they raise a defence of a practice generally prevailing and/or substantive legitimate expectation? The doctrine of legitimate expectation as a defence was authoritatively accepted as part of the South African administrative law in the landmark case of Administrator Transvaal v Traub. However, Chief Justice Corbett expressly stated in a dictum that the content of the expectation may be substantive or procedural in nature, [but] the protection of that expectation, if found to be legitimate, was exclusively procedural. It is argued that the dictum ignores section 33 of the Constitution which introduced reasonableness as an element of the right to just administrative action, which means that the substance of a decision may be reviewed if it is unreasonable. The objective is to examine whether the courts could develop the doctrine of legitimate expectation beyond the procedural protection, as already done in countries in Europe. Copyright / Dissertation (LLM)--University of Pretoria, 2012. / Mercantile Law / unrestricted

A disabled taxpayer, or a taxpayer caring for a disabled spouse or child, may deduct 100% of disability expenses from taxable income (section 18(2)(b) of the Income Tax Act No. 58 of 1962). For a 2010 year of assessment, disability expenses must meet the following three requirements to be deductible:  The expense should appear on the prescribed list.  It should have been necessarily incurred and paid for (and not recoverable) by the taxpayer.  It should have been incurred in consequence of any physical disability suffered by the taxpayer, his or her spouse or child, or any dependant of the taxpayer. If compared to a 2009 year of assessment, the second and third requirements remained the same. However, the prescribed list only became effective as from 1 March 2009 (i.e. as from the 2010 year of assessment). According to the discussion paper issued by SARS, the prescribed list was introduced to bring clarity as to the type of expenses that qualify and not to add another requirement. The expectation therefore arises that ALL expenses that meet the second and third requirements will appear on the prescribed list. The study explored the possible existence of an expense which had been necessarily incurred and paid by a South African taxpayer during his or her 2010 tax year in consequence of his or her disabled child, but which does not appear on the prescribed list. Data was collected by the researcher by using a questionnaire when having semistructured telephonic interviews with parents of severely disabled children. The results of the study indicate that there were indeed legitimate expenses incurred by the respondents during their 2010 year of assessment that did not appear on the prescribed list. The prescribed list therefore does not cater for all the possible legitimate expenses incurred by the parent of a severely disabled child. / Dissertation (MCom)--University of Pretoria, 2012. / Taxation / Unrestricted

Editorial

The application of accrual accounting principles is a challenge for public sectors internationally and increases the level of transparency and accountability of management. Taxation authorities are governed by legislation and have to be supported by a sound legislative framework to enable effective administration of taxes and the proper application of the accrual accounting principles. The recent issuing of the accounting standard for taxes and developments relating to the subsequent measurement of tax receivables highlights the ineffectiveness of current administrative tax legislation relating to penalties and interest which does not allow SARS to effectively apply accrual accounting principles. The receipt of taxpayer returns and payments as required by legislation are critical in order to allow the recording of taxes owed in the financial records of SARS. These taxpayer actions can only be effectively influenced by an effective penalty regime. Similarly, the current interest regimes on tax receivables and payables need to be adjusted in order to allow efficiencies and be comparative to market rates and calculation methods. International comparisons of penalty and interest regimes did not indicate a specific standard regime that should be applied, but the United Kingdom identified sound design principles for penalty and interest regimes. A simple standardised penalty and interest regime for all taxes administered by SARS is recommended which meets the identified design principles and supports the accrual accounting principles. The move to accrual accounting is an additional driver for administrative legislative reform which supports the effective management of taxation authorities. Copyright / Dissertation (MCom)--University of Pretoria, 2009. / Taxation / unrestricted

Como parte importante de la sociedad, las universidades forman un grupo activo que trabaja en la investigaciòn y el desarrollo de iniciativas que combaten el COVID-19

Background: Cancer patients are at higher risk of infection and severity of Coronavirus Disease-19 (COVID-19). Management of patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is challenging due to the scarce scientific information and treatment guidelines. In this work, we present our Institutional experience with our first 100 patients with oncological malignancies and COVID-19. Patients and methods: We conducted a cross-sectional study of the first 100 patients hospitalised at the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru) who were positive for SARS-CoV-2 by reverse transcriptase (RT)-PCR during the period 30 March to 20 June. Clinicopathological variables of the oncological disease as well as risk factors, management and outcomes to COVID-19 were evaluated. Results: The mean age was 43.5 years old (standard deviations: ±24.8) where 57% were male patients. In total, 44%, 37% and 19% were adult patients bearing solid tumours, adults with haematologic malignancies and paediatric patients, respectively. Hypertension was the most frequent comorbidity (23%) followed by chronic lung disease (10%). COVID-19-associated symptoms included cough (65%), fever (57%) and dyspnoea (56%). Twelve percent of patients were asymptomatic. Nosocomial infections were more frequent in paediatric patients (84.2%) than in adult patients (16.0%). Patients with uncontrolled oncological disease were most frequent (72%). Anaemia was present in 67% of patients, 68% had lymphopenia, 62% had ferritin value > 500 mcg/L, 85% had elevated lactate dehydrogenase (LDH), 83% D-dimer > 500 ng/mL and 80% C-Reactive Protein > 8 mg/L. The most common complication was acute respiratory failure (42%). Overall fatality rate was 39% where the main cause of mortality was acute respiratory distress syndrome (64.1%). Conclusion: Paediatric patients had better outcomes than adult populations, and a high number of asymptomatic carriers and nosocomial infection, early diagnosis are recommended. Considering oncological treatments 30 days before COVID-19 diagnosis, our data did not reveal an increased mortality. / Revisión por pares

Indiana University-Purdue University Indianapolis (IUPUI) / During 2020, the Indiana State Department of Health conducted a longitudinal study of novel severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus, the cause of COVID-19 disease, to understand the number of past and current infections as well as the prevalence of disease in the State of Indiana by conducting a survey to participants as well as administering testing for exposure to SARS-COV-2. The study consisted of 3 waves of testing, each spread months apart, consisting of a random sample and a non-random sample. The non-random sample was used to ensure the sample population was representative of the state of Indiana and was used as stratum in the logistic regression model, allowing for the adjustment for nonresponse. These finding indicate that persons of non-White race and persons of Hispanic ethnicity had highest risk of exposure to the virus. Understanding the disparity in health in various racial and ethnic populations and addressing how different communities are impacted by the pandemic, as well as working with the community is paramount when attempting to mitigate a pandemic. In addition, understanding the data from the ambient pandemic when instituting measures to mitigate the spread of viruses is also extremely important for managing health emergencies such as the COVID-19 pandemic.

After implementing a reliable mass spectrometry based kinetic study the indole conjugation with different organometallic indoles led to questions about the electronical and sterical influences on reactivity. The substitution pattern of the ferrocene functionalized indoles at the six-membered ring determines the electron density on the C3 atom, which reacts with the formed Schiff base. Since the experimental results showed the exact opposite trend, covalent docking studies were performed elucidating the importance of surface interactions. These studies were in harmony with the experimental results and determined lysine 33 as most preferable conjugation site as well as substitution in 6-position as most favourable pattern. The amine motif in compounds 6, 7 and 8 proofed to be easily fragmented by the ESI method used. The amide linker in 10 remains intact but shows a lower conversion. Those two inherent characteristics are however preferable for well-defined and site-specific bioconjugation. The synthesis and evaluation of piano stool complex derivatives with manganese and rhenium metal centre 15, 16, 18 and 22 gave additional guidance by the interpretation of applicable structural motifs. The electron-withdrawing carbonyl groups lead to the hindrance of fulvene formation and thus to no fragmentation as seen with the ferrocene group. The total conversion is low compared to 8, only 22 shows a good enough conversion to mainly monoconjugate of 45% and a possible radio-labelling application as 99mTc analogue. As consequence manganese complexes with a stable facial tricarbonyl unit and a tridentate chelator with 4-, 5- and 6-substituted aminomethylindole conjugated through an amide bond were synthesized and consecutively evaluated. The resulting organometallic indole derivatives 29, 30 and 31 all showed a total conversion around 40% similar to 16, but at the same time a rate constant in the range of 10-4 s-1 like the organic indole. Besides the similar conversion, the rate constants followed the trend of the 6-substituted derivative as fastest and then 5- and 4- substituted derivative with decreasing reactivity. For underlining the usage as technetium label for the best out of the series 31, a rhenium analogue was prepared. The resulting compound 32 was especially interesting, because the conversion was even higher than the 70% of 8 with a total of 88%. Additionally, the rate constant was a tenfold higher as well. This rendered compound 32 as best possible 99mTc analogue for further application as radio-label. After the success of 32 and realizing the sterical benefits resulting from the flexible tridentate ligand-system, substitution at the five-membered ring was explored. The complexes 33, 34 and 35 are based on indole-2-carboxylic acid and with the difference of the length of the alkyl spacer between amide and complex to probe for the influence and sterical hindrance, but all three derivatives showed no conjugation which excludes functionalization in 2-position. As the C3 is used for the actual bioconjugation, the last possible derivatization was realized on the indole-N1 by using 1-(3-bromopropyl)indole as building block during the synthesis of the ligand-system. The corresponding manganese 36 and rhenium 37 complexes both showed similar properties of a moderate conversion like 22 and a rate constant in the range of 10-5 s-1. In conclusion the rhenium complex 32 with the 6-substitution pattern at the tridentate indole-bearing ligand remains the most promising structure. The here developed liquid chromatography coupled mass spectrometry-based assay for the determination of inhibitory activity of drug candidates against the 3CLpro of the sever acute respiratory syndrome coronavirus type 2 was successfully implemented and especially designed to give, due to the available absorption spectra and corresponding mass traces, further insight in the otherwise through fluorescence resonance energy transfer-based assays neglected influences on the inhibition results. Starting with a literature-known quinolone containing covalent inhibitor 42 an N1-methylated derivative 43 and their analogues 44 and 45 in which the benzoic acid was exchanged for ferrocene carboxylic acid were synthesized. The inhibition of 3CLpro was evaluated by the concentration of initial 15mer peptide left after incubation and for that purpose the for 280 nm defined molar attenuation coefficient of (26.41±0.59) L*mol-1*cm-1 determined and used. The results showed a reaction of DL dithiothreitol with the less stable benzoic acid esters leading to a moderate inhibitory effect. The methylation in N1-position showed an increase in stability. The methylated and with ferrocene carboxylic acid functionalized derivative showed a complete inhibition during the timeframe of the assay. In search of a fluorescent and therefore traceable inhibitor, 4 hydroxycoumarin was used to synthesize the analogue with benzoic acid 49 and ferrocene carboxylic acid 50. Both derivatives were less stable than their analogues but exhibited the same trend of a more stable ferrocene-derived compound, which exerted a higher inhibition as well. After preparing and testing the model thioester 53 and showing an inactivation of the established inhibitor ebselen, it was concluded that the reaction with DL dithiothreitol reduces the concentration of active intact inhibitor and therefore decreases the inhibition rate during the assay. The next step was proofing the reducing agent as non-essential for the fast assay conducted in a timeframe of 5 min to circumvent the negative influence of DL dithiothreitol. By excluding every inhibition-altering part, the resulting method is the perfect tool for precise statements in relation of inhibitory activity. Then the inhibition assay was repeated for ebselen and the best out of the here introduced organometallic inhibitors 45. Both give equivalent results of a complete inhibition during the measurement. The implemented liquid chromatography coupled mass spectrometry-based assay has many advantages over the fluorescence resonance energy transfer-based assays in which all the information and insight accumulated by the evaluation of uv/vis traces and mass spectra are not available leading to wrong or deviating results regarding the inhibitory capacity of inhibitor candidates. / Nach der erfolgreichen Implementierung einer auf Massenspektrometrie basierenden Methode, um kinetische Studien über die Indolkonjugation durchzuführen, kamen Fragen über die elektronischen und sterischen Einflüsse auf die Reaktivität auf. Das Substitutionsmuster der Ferrocen-funktionalisierten Indole am sechsgliedrigen Ring bestimmt die Elektronendichte am C3-Atom, welches wiederum mit der zuvor entstandenen Schiffbase reagiert. Da die experimentellen Daten einen der Elektronendichte entgegengesetzten Trend aufwiesen, wurden Docking-Studien durchgeführt, um die Einflüsse der Wechselwirkungen mit der Proteinoberfläche näher zu beleuchten. Diese entsprachen den experimentellen Werten und zeigten, dass Lysin 33 die bevorzugte Konjugationsstelle ist und dass die Substitution in 6-Position die energetisch günstigste darstellt. Das sekundäre Amin der Verbindungen 6, 7 und 8 wurde unter den ESI-Bedingungen leicht fragmentiert. Die Amid-Bindung von 10 dagegen bleibt intakt und ein langsamerer Umsatz, welcher für einen wohl definierten Umsatz sorgt, wurde beobachtet. Die Synthese und Evaluation der Halbsandwich-Komplexe 15, 16, 18 und 22 gab zusätzlichen Aufschluss über die strukturellen Einflüsse. Die elektronenziehenden Carbonyle behindern die Bildung der Fulvene, welche für die Ferrocen-Derivate beobachtet worden war. Der Gesamtumsatz ist vergleichsweise gering und nur Substanz 22 zeigt eine annehmbare Konversion von 45% an Monokonjugat auf, welches sie wiederum für den Einsatz als 99mTc-Analog qualifiziert. Als direkte Konsequenz wurden Mangankomplexe mit einer stabilen facialen Tricarbonyl-Einheit und einem Indol beinhaltenden tridentaten Liganden synthetisiert. Dies wurde für die 4-, 5- und 6-Substitution durchgeführt um die Komplexe 29, 30 und 31 zu erhalten. Alle drei zeigten eine Konversion von ungefähr 40% und lagen mit einer Ratenkonstante von 10-4 s-1 in dem Bereich des organischen Indols. Die Ratenkonstanten folgten hingegen wiederum dem Trend der begünstigten 6-Position, gefolgt von der 5- und dann 4-Position. Um einen Verglich zu einer analogen Technetium-Verbindung zu ziehen wurde der beste Komplex 31 als Rhenium-Analog 32 hergestellt. Dies wies den bisher höchsten Gesamtumsatz von 88% auf, welches die Konversion von 70% der Verbindung 8 überschritt. Dadurch qualifizierte sich Verbindung 32 als beste Option für eine Umsetzung als Radiomarker. Nach den Erkenntnissen über die begünstigte Sterik der flexiblen tridendaten Liganden wurde versucht den Erfolg auf den Fünfring zu übertragen. Eine auf Indol-2-säure basierende Reihe an Komplexen (33,34,35) mit unterschiedlich langen Alkyl-Ketten zwischen Indol und Metallkomplex sollte Aufschluss über den sterischen Anspruch geben, allerdings war keine Konjugation für alle drei Derivate zu beobachten. Als Konsequenz wurde die 2-Position für weitere Funktionalisierung nicht weiter berücksichtigt. Die letzte verbliebene Stelle war das Indol-amin selbst, welche durch den Einsatz von 1-(3-bromopropyl)indol bei der Ligandensynthese erfolgreich alkyliert wurde. Der resultierende Mangan- 36 und Rhenium-Komplex 37 zeigten eine mit 22 vergleichbare moderate Konversion und um eine Größenordnung kleinere Ratenkonstante. Durch diese Erkenntnisse verblieb der Rhenium-Komplex 32 weiterhin der beste Kandidat für eine Umsetzung als radioaktiver Marker. Der hier beschriebene liquid chromatography coupled mass spectrometry basierte Assay für die Bestimmung der Inhibitions-Wirkung gegenüber der 3CLpro des sever acute respiratory syndrome coronavirus type 2 wurde erfolgreich etabliert. Durch die zusätzlichen Absorptions , sowie Massenspektren wurden weitere Informationen gewonnen, welche in den oft angewendeten Fluoreszenz-Resonanzenergietransfer Assays vernachlässigt werden und zu Verfälschungen der Inhibitionsergebnisse führen. Ausgehend von dem literaturbekannten kovalenten Inhibitor 42 wurde ein N1-methyliertes Derivat 43 hergestellt. Durch den Austausch von Benzoesäure durch Ferrocensäure wurden die Analoge 44 und 45 erhalten. Die Restkonzentration des 15mer Substrats nach der Inkubation wurde als Maß der Inhibition herangezogen. Hierfür wurde der molare Extinktionskoeffizient bei 280 nm mit (26.41±0.59) L*mol-1*cm-1 bestimmt. Die Methylierung führte zu einer erhöhten Stabilität. Der Wirkstoffkandidat 45 zeigte außerdem eine vollständige Inhibition im Rahmen des durchgeführten Assays. 4-Hydroxycoumarin wurde verwendet, um die fluoreszenten Analoga 49 und 50 herzustellen. Beide waren instabiler, wobei das Ferrocen-Derivat wie zuvor eine erhöhte Inhibition aufzeigte. Nach der Synthese und Auswertung des Assays für eine Thioester Modellverbindung 53 und einer nachgewiesenen Inaktivierung des etablierten Inhibitors Ebselen wurden die Nebenreaktionen mit DL-Dithiothreitol als Ursache für einen Konzentrationsabfall der aktiven und intakten Inhibitoren und infolgedessen verringerte Inhibition angenommen. Als nächstes wurde bewiesen, dass der Zusatz eines Reduktionsmittels wie keinen Einfluss auf die Enzymaktivität während des kurzen Assays hat. So wurden alle Einflüsse auf die Inhibitionswirkung ausgeschlossen und der nun makellose Assay für Ebselen und den hier vorgestellten neuartigen organometallischen Inhibitor 45 wiederholt, welche beide eine vollständige Inhibition aufwiesen.