Event-related functional magnetic resonance imaging of reward-related brain circuitry in children and adolescents

BACKGROUND: Functional disturbances in reward-related brain systems are thought to play a role in the development of mood, impulse, and substance abuse disorders. Studies in non-human primates have identified brain regions, including the dorsal / ventral striatum and orbital-frontal cortex (OFC), in which neural activity is modulated by reward. Recent studies in adults have concurred with these findings by observing reward-contingent blood oxygen level dependant (BOLD) responses in these regions during functional magnetic resonance imaging (FMRI) paradigms. However no previous studies indicate whether comparable modulations of neural activity exist in the brain reward systems of children and adolescents. METHODS: We used event-related FMRI and a behavioral paradigm modeled on previous work in adults to study brain responses to monetary gains and losses in non-psychiatric children and adolescents as part of a program examining the neural substrates of anxiety and depression in youth. RESULTS: Regions and time-courses of reward-related activity were similar to those observed in adults with condition-dependent BOLD changes in the ventral striatum, lateral and medial OFC; specifically, these regions showed larger responses to positive than to negative feedback. CONCLUSIONS: These results provide further evidence for the value of event-related FMRI in examining reward systems of the brain, demonstrate the feasibility of this approach in children and adolescents, and establish a baseline from which to understand the pathophysiology of reward-related psychiatric disorders in youth

The in vitro and in vivo testing of chemotherapeutic agents against pathogenic free living amebae : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Microbiology at Massey University, Palmerston North, New Zealand.

During the last ten years, there has been an increasing awareness of sporadic cases of Primary Amoebic Meningo-encephalitis (PAM) affecting primarily younger age groups and appearing in an acute fulminant form. The earliest positive case (Willaert, 1974) may have been in England in 1909 which shows that the disease has been with us for a long time. The pathogenic free-living amebae (PFLA), which comprises the genus Naegleria and the genus Acanthamoeba, are the causative organisms of PAM and AM*respectively. PAM is a rapidly fatal disease affecting the central nervous system (CNS),the treatment of which to date has been successful in only a small number of cases, and therefore the continual screening of suitable chemotherapeutic agents against amebae of the Naegleria spp. and Acanthamoeba spp., is of great importance. AM is also essentially confined to the CNS although it may take the form of chronic granulomata in the liver, spleen, uterus and kidneys (Martinez et al., 1977). Six chemotherapeutic agents: Amphotericin B, 5-Fluorocytosine, Kanamycin, Oxytetracycline, Tylosine and Levamisole were tested for activity against a non-pathogenic and a pathogenic species of Naegleria and a non-pathogenic and a pathogenic species of Acanthamoeba in axenic culture. For the Naegleria spp., Amphotericin B and Oxytetracycline were found to be active and the Acanthamoeba spp. were found to be only susceptible to Levamisole. The synergistic combinations of drugs against the amebae were also investigated in axenic culture. In preliminary trials Kanamycin together with Oxytetracycline showed promise against Naegleria fowleri (MsM) but this was later shown not to be the case. Amphotericin B in combination with 5-Fluorocytosine was also shown not to be synergistic, however Amphotericin B in combination with Oxytetracycline proved to be effective against N. fowleri. Amphotericin B was combined with 5-Fluorocytosine against A. culbertsoni (A-1) but was not found to be synergistically active. * Amebic meningitis caused by Acanthamoeba infections. Levamisole was also tested against N. gruberi (P1200f) and A. castellanii (0.1) at various stages in growth of the amebae (i.e. 24, 48 and 72 hour stock cultures) to determine the effect of using aged amebae. It was found that the age of the stock culture bore no relation to the activity of the drug. After axenic culture testing, the susceptibility of the pathogenic N. fowleri (MsM) and A. culbertsoni (A-1) to the agents which showed activity, was investigated in a vero cell culture system. For N. fowleri (MsM) the results of axenic culture testing were confirmed, with Amphotericin B and Oxytetracycline protecting the monolayer from the destructive effects of the amebae, both when used singly and at a greater efficiency when added together as a synergistic combination. Levamisole, although effective to some extent against Acanthamoeba spp. in axenic culture, failed to show any activity against the amebae in vero cell culture testing. In vivo animal protection studies were then performed using drugs that had been shown either in this or other studies to be effective against either Naegleria or Acanthamoeba spp. Chemotherapeutic agents tested on N. fowleri (MsM) included two imidazoles; Miconazole nitrate and Ketoconazole (previously known as R41,400), as well as Amphotericin B. The synergistic combination of Amphotericin B with either Tetracycline or Oxytetracycline was also investigated. For A. culbertsoni (A-1), 5-Fluorocytosine, and Polymyxin B were tried both singly and in combination. These drugs were injected by intraperitoneal (I.P.) and intraventricular (I.vent.) routes. The results were not promising, with none of the drugs offering significant protection even whilst using Amphotericin B which is considered the drug of choice. The question of adequate drug levels reaching the brain was tested out with two imidazoles, Ketoconazole and Miconazole. Serum samples were assayed against Candida pirapsilosis and C. pseudotropicalis respectively at various time intervals after innoculation with the drug, and a gradual increase and breakdown of the drug in the animal system could then be shown. These results showed that based on in vitro results, the levels of the imidazoles obtained in the serum after the first eight hours after injection, should have been sufficiently high to prevent amebic multiplication

An approach to a field drainage problem by laboratory examination of selected properties of undisturbed soil cores : thesis presented at Massey University of Manawatu in part fulfilment of the requirements for the degree of Master of Agricutural Science

For many years, soil drainage investigators, from a practical view point, have had to content themselves with expert appraisal of certain direct and indirect soil and environmental characteristics in order to ascertain the cause of a particular drainage problem. In a great many instances, observations of vegetative composition, topography and general soil type, aided by aerial photography and local experience, give completely adequate information. Normally, derivation of conclusions from such observations is based on well established principles, and the recognition of general broad classes of the cause of mal-drainage conditions. Such classes may be grouped as; (I) where infiltration capacity of a soil is inadequate to deal with the amount of water supplied to the surface, because of topography, abnormal rainfall, or through inherent inability of the soil to transmit water internally, (II) where the groundwater table rises to a height detrimental to vegetative survival and/or soil structure, or where its presence hinders the function of a free draining subsoil, end (III) where a similar situation exists, due to a perched or elevated ground-water table. The allocation of a particular drainage problem to one or more of these broad classes is not usually difficult, but identification of causal processes within classes presents quite another problem. Often, drainage investigators have been content to evolve general treatments for each class, and, as a basic rule, such procedures have, more often than not, proved reasonably effective. However, with the increasing intensification of pastoral and agricultural farming, the fundamental causes of individual mal-drainage conditions must be positively identified and rectified within the broadly classified groups

Novel screening methods for the detection of Yersinia enterocolitica in infected blood used for transfusion : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Microbiology at Massey University

Between 1991-1996, 8 patients experienced rare life-threatening reactions that followed the transfusion of blood infected with Yersinia enterocolitica. The first reported case occurred in 1991 and was followed by seven others that directly caused or contributed to the death of 5 of 8 patients. Y. enterocolitica is a food and water borne infection of the gastrointestinal tract which in adults is often asymptomatic. An unknown number of those infected experience a period of self-limiting bacteraemia. The large volume of blood collected during donation phlebotomy may contain small numbers of bacteria that can increase in number during blood bank storage, producing potentially lethal levels of bacteria and toxin. Currently there are no reliable methods available to distinguish blood donations that present the greatest risk from those that present little risk. This thesis, reports on the evaluation of two techniques to prevent the transfusion of blood infected with Y. enterocolitica. The first, a molecular method, was used to amplify bacterial DNA in blood by Polymerase Chain Reaction (PCR). A 425 bp product was amplified from DNA extractions of infected blood. Results showed that the technical complexities of the methodology, together with poor sensitivity and the need for large-scale donation sampling make PCR as applied for this purpose unattractive. An Enzyme Linked Immunosorbent Assay was developed to detect current/recent infection with Y. enterocolitica in healthy blood donors. Polystyrene beads were coated with bacterial proteins to detect IgA antibody to Y. enterocolitica in human serum. The sera from donors of confirmed unit infections, paired sera from culture-proven Y. enterocolitica gastrointestinal tract infection and sera from volunteer blood donors were tested. Results showed that the sera of six bacteraemic blood donors tested contained elevated levels of IgA antibody. High rates of positivity (26/27), were detected in sera from culture-confirmed GIT infection and a rate of 4.04% seropositivity was found among 495 blood donors enrolled in a clinical trial. Results showed a strong correlation between IgA seropositivity, and recipient risk associated with the transfusion of blood heavily infected with Y. enterocolitica. The work demonstrated how the use of a simple screening test for recent infection, could be used to exclude high risk donations and improve the safety of blood transfusion in New Zealand

The cumulative effects of seven days of imposed exercise on energy balance and appetite regulation

A thesis submitted to the University of Bedfordshire, in fulfilment of the requirements for the degree of MSc by ResearchIncreasing energy expenditure (EE) through regular exercise is a promising strategy to prevent body fat gain. However, imposed exercise interventions often produce weight loss that is less than theoretically expected, possibility due to compensatory mechanisms in energy intake (EI) and EE. Study one was designed to determine whether a combined written and photographic food diary was a reliable measure of EI within a free-living environment across seven days. The results suggested this method was reliable at the group level. However, 95% limits of agreement (LoA) showed large variability (-1258 to 1545 kcal/day) at the individual level. Study two investigated acylated ghrelin, PYY and energy balance in response to 7-days of imposed exercise and a control condition. EI increased by 511 kcal/day in the exercise condition (P=0.005). Late-postprandial acylated ghrelin concentrations were higher in the exercise condition (P=0.072), but did not change from pre- to post intervention. There was a larger, but non-significant, increase in EI at the postprandial ad libitum pasta meal in the exercise condition (P=0.285). In conclusion, 7-days exercise resulted in increased EI under free-living conditions; similar results were found when assessed in a controlled laboratory environment. A larger sample size would allow confirmation of the findings

Using oxygen isotope analysis and a multi-isotopic approach in determining the region of origin of human remains

Multi-isotopic approaches have been used effectively to help provide estimated geographic origins for unidentified skeletal remains in cold case homicides and archaeological contexts, when DNA testing was not practical. Stable oxygen and strontium isotopes were used in the present study in order to determine their effectiveness of proveniencing human remains from Colombia and New England. Enamel hydroxyapatite was extracted from individual teeth (n=151) from individuals with known birthplaces for different regions of Colombia as well as the region of New England in the United States. All oxygen data is presented as a ratio of δ18O /δ16O (‰PDB). The results show significant geographical differences (p ≤ 0.001), between the Colombian and New England populations. The mean δ18O value for Colombia is -11.06 ± 1.28. The mean 87Sr/86Sr value for Colombia is 0.707391 ± 0.0016. The mean δ18O value of the samples from the United States is -7.42 ± 1.39. The mean 87Sr/86Sr value for the samples from the United States is 0.7099747 ± 0.0011. The oxygen and strontium ratios of the sample set have no significant differences within each geographic region. Additionally, a small subset of the immigrant community in Boston, MA is represented within the sample. There is a significant difference (p ≤ 0.002) in the population’s mean δ18O values. The establishment of this oxygen and strontium isoscape has the potential to provenience unidentified human remains recovered as a result of Colombia’s long-term internal conflict

Reversible Peg Solitaire on Graphs

The game of peg solitaire on graphs was introduced by Beeler and Hoilman in 2011. In this game, pegs are initially placed on all but one vertex of a graph G. If xyz forms a path in G and there are pegs on vertices x and y but not z, then a jump places a peg on z and removes the pegs from x and y. A graph is called solvable if, for some configuration of pegs occupying all but one vertex, some sequence of jumps leaves a single peg. We study the game of reversible peg solitaire, where there are again initially pegs on all but one vertex, but now both jumps and unjumps (the reversal of a jump) are allowed. We show that in this game all non-star graphs that contain a vertex of degree at least three are solvable, that cycles and paths on n vertices, where n is divisible by 2 or 3, are solvable, and that all other graphs are not solvable. We also classify the possible starting hole and ending peg positions for solvable graphs