Applying a Dynamical Systems Model and Network Theory to Major Depressive Disorder

Mental disorders like major depressive disorder can be seen as complex dynamical systems. In this study we investigate the dynamic behaviour of individuals to see whether or not we can expect a transition to another mood state. We introduce a mean field model to a binomial process, where we reduce a dynamic multidimensional system (stochastic cellular automaton) to a one-dimensional system to analyse the dynamics. Using maximum likelihood estimation, we can estimate the parameter of interest which, in combination with a bifurcation diagram, reflects the expectancy that someone has to transition to another mood state. After validating the proposed method with simulated data, we apply this method to two empirical examples, where we show its use in a clinical sample consisting of patients diagnosed with major depressive disorder, and a general population sample. Results showed that the majority of the clinical sample was categorized as having an expectancy for a transition, while the majority of the general population sample did not have this expectancy. We conclude that the mean field model has great potential in assessing the expectancy for a transition between mood states. With some extensions it could, in the future, aid clinical therapists in the treatment of depressed patients.Comment: arXiv admin note: text overlap with arXiv:1610.0504

Structural and synthetic studies of sesquiterpenoids and flavonoids isolated from Helichrysum species

Thesis (Ph.D.) - University of KwaZulu-Natal, Pietermaritzburg, 2008.The genus Helichrysum (Asteraceae) consists of approximately 500 species worldwide, with 245 indigenous to South Africa. As a result of the large number of species, the chemistry and biological activity of several species have not yet been investigated. The aim of this project was to investigate the phytochemistry of three species and propose a synthetic route to one of the antibacterial compounds isolated. An extensive literature review regarding the widespread traditional uses, biological activity and phytochemistry of the South African Helichrysum species is provided. From Helichrysum splendidum, a plant used traditionally to treat rheumatism, two monomeric guaianolides and a dimeric guaianolide, helisplendidilactone, were isolated. The stereochemistry of these known compounds was confirmed and the NMR assignments for certain peaks of helisplendidilactone were corrected. An X-ray structure for helisplendidilactone was obtained for the first time. The phytochemistry of Helichrysum montanum was investigated for the first time and new diastereoisomers of known guaianolides were isolated. The phytochemistry of H. splendidum and H. montanum is remarkably similar and supports their morphological classification in the same taxonomic group. The chloroform:methanol extract of H. montanum yielded a new dimeric guaianolide, 13’-epihelisplendidilactone, which is related to helisplendidilactone, as well as three monomeric guaianolides (of which one is a new diastereomer of a known compound). The extract also yielded spathulenol (a sesquiterpene), umbelliferone (a coumarin) and 4’,5,7-trihydroxy-3,3’,8-trimethoxyflavone (a flavonoid). Thirty-five Helichrysum species were screened for antimicrobial activity against six microorganisms and a preliminary cytotoxic assay, which included the use of “normal” and cancer cell lines, was performed. H. excisum was selected for further study based on the fact that it exhibited promising antimicrobial activity and relative low toxicity. Furthermore, with the exception of the essential oil, the phytochemistry of this species has not been investigated. From the aerial parts of H. excisum, five flavonoids, identified as pinocembrin, gnaphaliin, lepidissipyrone, 5-hydroxy-7,8-dimethoxyflavone and isoscutellarein 7-O-b-glucoside were isolated. Four of these flavonoids have an unsubstituted B-ring, a phenomenon often observed in flavonoids isolated from Helichrysum species. The active antimicrobial component of H. excisum has been identified as lepidissipyrone. Owing to the interesting biological activities reported for phloroglucinol a-pyrones and the synthetic challenges associated with these molecules, lepidissipyrone was selected for a synthetic study. Both the flavanone and pyrone moieties present in lepidissipyrone have been successfully synthesised. A successful strategy towards the CH2 linker between the two units has been illustrated. The strategy could be used to synthesise similar phloroglucinol-derived pyrones

On the Cause of the Mid‐Pleistocene Transition

The Mid-Pleistocene Transition (MPT), where the Pleistocene glacial cycles changed from 41 to ∼100 kyr periodicity, is one of the most intriguing unsolved issues in the field of paleoclimatology. Over the course of over four decades of research, several different physical mechanisms have been proposed to explain the MPT, involving non-linear feedbacks between ice sheets and the global climate, the solid Earth, ocean circulation, and the carbon cycle. Here, we review these different mechanisms, comparing how each of them relates to the others, and to the currently available observational evidence. Based on this discussion, we identify the most important gaps in our current understanding of the MPT. We discuss how new model experiments, which focus on the quantitative differences between the different physical mechanisms, could help fill these gaps. The results of those experiments could help interpret available proxy evidence, as well as new evidence that is expected to become available

Flow-volume curves as measurement of respiratory mechanics during ventilatory support:The effect of the exhalation valve

Objective: To assess the feasibility of expiratory flow-volume curves as a measurement of respiratory mechanics during ventilatory support: to what extent is the shape of the curve affected by the exhalation valve of the ventilator? Design: Prospective, comparative study. Setting: Medical intensive care unit of a university hospital. Patients: 28 consecutive patients with various conditions, mechanically ventilated with both the Siemens Servo 900C and 300 ventilators, were studied under sedation and paralysis. Interventions: The ventilator circuit was intermittently disconnected from the ventilator at end-inspiration in order to obtain flow-volume curves with and without the exhalation valve in place. Measurements and results: Peak flow (PEF) and the slope of the flow-volume curve during the last 50% of expired volume (SF50) were obtained both with and without the exhalation valve in place. The exhalation valve caused a significant reduction in peak flow of 0.3 l/s (from 1.27 to 0.97 l/s) with the Siemens Servo 900 C ventilator and of 0.42 l/s (from 1.36 to 0.94 l/s) with the Siemens Servo 300 ventilator (p &lt; 0.001). The SF50 was not affected. Conclusion: In mechanically ventilated patients, the exhalation valve causes a significant reduction in peak flow, but does not affect the SF50. This study further suggests that the second part of the expiratory flow-volume curve can be used to estimate patients' respiratory mechanics during ventilatory support.</p

On the Cause of the Mid-Pleistocene Transition

The Mid-Pleistocene Transition (MPT), where the Pleistocene glacial cycles changed from 41 to ∼100 kyr periodicity, is one of the most intriguing unsolved issues in the field of paleoclimatology. Over the course of over four decades of research, several different physical mechanisms have been proposed to explain the MPT, involving non-linear feedbacks between ice sheets and the global climate, the solid Earth, ocean circulation, and the carbon cycle. Here, we review these different mechanisms, comparing how each of them relates to the others, and to the currently available observational evidence. Based on this discussion, we identify the most important gaps in our current understanding of the MPT. We discuss how new model experiments, which focus on the quantitative differences between the different physical mechanisms, could help fill these gaps. The results of those experiments could help interpret available proxy evidence, as well as new evidence that is expected to become available

On the duration of magnetochrons C24r and C25n and the timing of early Eocene global warming events: Implications from the Ocean Drilling Program Leg 208 Walvis Ridge depth transect

Five sections drilled in multiple holes over a depth transect of more than 2200 m at the Walvis Ridge (SE Atlantic) during Ocean Drilling Program (ODP) Leg 208 resulted in the first complete early Paleogene deep-sea record. Here we present high-resolution stratigraphic records spanning a ~4.3 million yearlong interval of the late Paleocene to early Eocene. This interval includes the Paleocene-Eocene thermal maximum (PETM) as well as the Eocene thermal maximum (ETM) 2 event. A detailed chronology was developed with nondestructive X-ray fluorescence (XRF) core scanning records and shipboard color data. These records were used to refine the shipboard-derived spliced composite depth for each site and with a record from ODP Site 1051 were then used to establish a continuous time series over this interval. Extensive spectral analysis reveals that the early Paleogene sedimentary cyclicity is dominated by precession modulated by the short (100 kyr) and long (405 kyr) eccentricity cycles. Counting of precession-related cycles at multiple sites results in revised estimates for the duration of magnetochrons C24r and C25n. Direct comparison between the amplitude modulation of the precession component derived from XRF data and recent models of Earth’s orbital eccentricity suggests that the onset of the PETM and ETM2 are related to a 100-kyr eccentricity maximum. Both events are approximately a quarter of a period offset from a maximum in the 405-kyr eccentricity cycle, with the major difference that the PETM is lagging and ETM2 is leading a 405-kyr eccentricity maximum. Absolute age estimates for the PETM, ETM2, and the magnetochron boundaries that are consistent with recalibrated radiometric ages and recent models of Earth’s orbital eccentricity cannot be precisely determined at present because of too large uncertainties in these methods. Nevertheless, we provide two possible tuning options, which demonstrate the potential for the development of a cyclostratigraphic framework based on the stable 405-kyr eccentricity cycle for the entire Paleogene

Case studies: Tuberculination in pig herds suspected of infection with Mycobacterium avium

Mycobacterium avium, both subspecies hominissuis (MAH) and subsp avium (MAA), are considered a significant zoonotic hazard in pigs. Therefore special attention is given to detect the presence of this hazard in pigs during post mortem meat inspection. Herds delivered at slaughter were monitored on blood antibodies against MAH. Herds with an antibody response against a MAH infection were visited. Initially a questionnaire assessing relevant risk factors for MAH was applied