Does nuclear tissue infected with bacteria following disc herniations lead to Modic changes in the adjacent vertebrae?

Purpose To investigate the prevalence of infected herniated nucleus material in lumbar disc herniations and to determine if patients with an anaerobic infected disc are more likely to develop Modic change (MC) (bone oedema) in the adjacent vertebrae after the disc herniation. MCs (bone oedema) in vertebrae are observed in 6 % of the general population and in 35-40 % of people with low back pain. These changes are strongly associated with low back pain. There are probably a mechanical cause and an infective cause that causes MC. Several studies on nuclear tissue from herniated discs have demonstrated the presence of low virulent anaerobic microorganisms, predominantly Propionibacterium acnes, in 7-53 % of patients. At the time of a herniation these low virulent anaerobic bacteria may enter the disc and give rise to an insidious infection. Local inflammation in the adjacent bone may be a secondary effect due to cytokine and propionic acid production. Methods Patients undergoing primary surgery at a single spinal level for lumbar disc herniation with an MRI-confirmed lumbar disc herniation, where the annular fibres were penetrated by visible nuclear tissue, had the nucleus material removed. Stringent antiseptic sterile protocols were followed. Results Sixty-one patients were included, mean age 46.4 years (SD 9.7), 27 % female. All patients were immunocompetent. No patient had received a previous epidural steroid injection or undergone previous back surgery. In total, microbiological cultures were positive in 28 (46 %) patients. Anaerobic cultures were positive in 26 (43 %) patients, and of these 4 (7 %) had dual microbial infections, containing both one aerobic and one anaerobic culture. No tissue specimens had more than two types of bacteria identified. Two (3 %) cultures only had aerobic bacteria isolated. In the discs with a nucleus with anaerobic bacteria, 80 % developed new MC in the vertebrae adjacent to the previous disc herniation. In contrast, none of those with aerobic bacteria and only 44 % of patients with negative cultures developed new MC. The association between an anaerobic culture and new MCs is highly statistically significant (P = 0.0038), with an odds ratio of 5.60 (95 % CI 1.51-21.95). Conclusion These findings support the theory that the occurrence of MCs Type 1 in the vertebrae adjacent to a previously herniated disc may be due to oedema surrounding an infected disc. The discs infected with anaerobic bacteria were more likely (P<0.0038) to develop MCs in the adjacent vertebrae than those in which no bacteria were found or those in which aerobic bacteria were found. © Springer-Verlag Berlin Heidelberg 2013.

An exploratory study of management accounting and control systems in a developing country

This thesis reports on the results of case studies in four commercial banks in Nigeria. The study focuses how management accounting and control systems (MCS) operate in the four banks. The study is motivated by the dearth of literature on management accounting practices in the developing world in general and in Nigeria in specific. The case study approach adopted in conducting the research was useful in exploring the dynamics of the MCS in the organisations. Data was gathered from two sources. First, semi-structured interviews were conducted with managers at the head office, regional office and branches of each bank. The participants were selected from different backgrounds and managerial levels to provide broader understanding of the operations of the MCS. Second, various internal and external documents were reviewed to provide supporting evidence for the interview results. New institutional sociology (NIS) provided the theoretical framework to understand the results. NIS provided explanations for how the MCS in the four banks were shaped by diverse external and internal factors. The key factors identified as shaping the operations of the MCS were the need to comply with the regulatory environment (coercive isomorphism), the need to maintain social and cultural support (normative isomorphism) and the need to imitate successful organisations in order to appear legitimate (mimetic isomorphism). The study also examines the interplay between the institutional forces, market forces and infra-organisational power relations. This analysis is necessary to overcome the criticism of NIS that it downplays the role of market forces, agency and intra-organisational relations. The findings of the study have implications for understanding the operations of MCS in the developing world.

The relationship between alexithymia and salivary cortisol levels in somatoform disorders

The purpose of this study was to investigate cortisol levels as a function of the hypothalamic-pituitary-adrenal axis (HPA) in relation to alexithymia in patients with somatoform disorders (SFD). Diurnal salivary cortisol was sampled in 32 patients with SFD who also underwent a psychiatric examination and filled in questionnaires (Toronto Alexithymia Scale, TAS scale; Screening for Somatoform Symptoms, SOMS scale; Hamilton Depression Scale, HAMD). The mean TAS total score in the sample was 55.69.6, 32% of patients being classified as alexithymic on the basis of their TAS scores. Depression scores were moderate (HAMD=13.2, Beck Depression Inventory, BDI=16.5). The patients' alexithymia scores (TAS scale Difficulty identifying feelings) correlated significantly positively with their somatization scale scores (Symptom Checklist-90 Revised, SCL-90-R); r=0.3438 (P0.05) and their scores on the Global Severity Index (GSI) on the SCL-90-R; r=0.781 (P0.01). Regression analysis was performed with cortisol variables as the dependent variables. Cortisol levels [measured by the area under the curve-ground (AUC-G), area under the curve-increase (AUC-I) and morning cortisol (MCS)] were best predicted in a multiple linear regression model by lower depressive scores (HAMD) and more psychopathological symptoms (SCL-90-R). No significant correlations were found between the patients' alexithymia scores (TAS) and cortisol levels. The healthy control group (n=25) demonstrated significantly higher cortisol levels than did the patients with SFD; in both tests P0.001 for AUC-G and AUC-I. However, the two groups did not differ in terms of their mean morning cortisol levels (P0.05). The results suggest that pre-existing hypocortisolism might possibly be associated with SFD.

Structure-activity relationships of the N-terminus of calcitonin gene-related peptide:key roles of alanine-5 and threonine-6 in receptor activation

Background and purpose - The N-terminus of calcitonin gene-related peptide (CGRP) is important for receptor activation, especially the disulphide-bonded ring (residues 1-7). However, the roles of individual amino acids within this region have not been examined and so the molecular determinants of agonism are unknown. This study has examined the role of residues 1, 3-6 and 8-9, excluding Cys-2 and Cys-7. Experimental approach - CGRP derivatives were substituted with either cysteine or alanine; further residues were introduced at position 6. Their affinity was measured by radioligand binding and their efficacy by measuring cAMP production in SK-N-MC cells and ß-arrestin 2 translocation in CHO-K1 cells at the CGRP receptor. Key results - Substitution of Ala-5 by cysteine reduced affinity 270-fold and reduced efficacy for production of cAMP in SK-N-MCs. Potency at ß-arrestin translocation was reduced by 9-fold. Substitution of Thr-6 by cysteine destroyed all measurable efficacy of both cAMP and ß-arrestin responses; substitution with either alanine or serine impaired potency. Substitutions at positions 1, 4, 8 and 9 resulted in approximately 10-fold reductions in potency at both responses. Similar observations were made at a second CGRP-activated receptor, the AMY1(a) receptor. Conclusions and implications - Ala-5 and Thr-6 are key determinants of agonist activity for CGRP. Ala-5 is also very important for receptor binding. Residues outside of the 1-7 ring also contribute to agonist activity.

Connection of Network Sensors to Distributed Information Measurement and Control System for Education and Research

The development of the distributed information measurement and control system for optical spectral research of particle beam and plasma objects and the execution of laboratory works on Physics and Engineering Department of Petrozavodsk State University are described. At the hardware level the system is represented by a complex of the automated workplaces joined into computer network. The key element of the system is the communication server, which supports the multi-user mode and distributes resources among clients, monitors the system and provides secure access. Other system components are formed by equipment servers (CАМАC and GPIB servers, a server for the access to microcontrollers MCS-196 and others) and the client programs that carry out data acquisition, accumulation and processing and management of the course of the experiment as well. In this work the designed by the authors network interface is discussed. The interface provides the connection of measuring and executive devices to the distributed information measurement and control system via Ethernet. This interface allows controlling of experimental parameters by use of digital devices, monitoring of experiment parameters by polling of analog and digital sensors. The device firmware is written in assembler language and includes libraries for Ethernet-, IP-, TCP- и UDP-packets forming.

The risk of re-intervention after endovascular aortic aneurysm repair

This thesis studies survival analysis techniques dealing with censoring to produce predictive tools that predict the risk of endovascular aortic aneurysm repair (EVAR) re-intervention. Censoring indicates that some patients do not continue follow up, so their outcome class is unknown. Methods dealing with censoring have drawbacks and cannot handle the high censoring of the two EVAR datasets collected. Therefore, this thesis presents a new solution to high censoring by modifying an approach that was incapable of differentiating between risks groups of aortic complications. Feature selection (FS) becomes complicated with censoring. Most survival FS methods depends on Cox's model, however machine learning classifiers (MLC) are preferred. Few methods adopted MLC to perform survival FS, but they cannot be used with high censoring. This thesis proposes two FS methods which use MLC to evaluate features. The two FS methods use the new solution to deal with censoring. They combine factor analysis with greedy stepwise FS search which allows eliminated features to enter the FS process. The first FS method searches for the best neural networks' configuration and subset of features. The second approach combines support vector machines, neural networks, and K nearest neighbor classifiers using simple and weighted majority voting to construct a multiple classifier system (MCS) for improving the performance of individual classifiers. It presents a new hybrid FS process by using MCS as a wrapper method and merging it with the iterated feature ranking filter method to further reduce the features. The proposed techniques outperformed FS methods based on Cox's model such as; Akaike and Bayesian information criteria, and least absolute shrinkage and selector operator in the log-rank test's p-values, sensitivity, and concordance. This proves that the proposed techniques are more powerful in correctly predicting the risk of re-intervention. Consequently, they enable doctors to set patients’ appropriate future observation plan.

Mechanistic studies on the advanced oxidation and photochemical transformation of cyanotoxins (microcystins)

The increased occurrence of cyanobacteria (blue-green algae) blooms and the production of associated cyanotoxins have presented a threat to drinking water sources. Among the most common types of cyanotoxins found in potable water are microcystins (MCs), a family of cyclic heptapeptides containing substrates. MCs are strongly hepatotoxic and known to initiate tumor promoting activity. The presence of sub-lethal doses of MCs in drinking water is implicated as one of the key risk factors for an unusually high occurrence of primary liver cancer. ^ A variety of traditional water treatment methods have been attempted for the removal of cyanotoxins, but with limited success. Advanced Oxidation Technologies (AOTs) are attractive alternatives to traditional water treatments. We have demonstrated ultrasonic irradiation and UV/H2O2 lead to the degradation of cyanotoxins in drinking water. These studies demonstrate AOTs can effectively degrade MCs and their associated toxicity is dramatically reduced. We have conducted detailed studies of different degradation pathways of MCs and conclude that the hydroxyl radical is responsible for a significant fraction of the observed degradation. Results indicate preliminary products of the sonolysis of MCs are due to the hydroxyl radical attack on the benzene ring and substitution and cleavage of the diene of the Adda peptide residue. AOTs are attractive methods for treatment of cyanotoxins in potable water supplies. ^ The photochemical transformation of MCs is important in the environmental degradation of MCs. Previous studies implicated singlet oxygen as a primary oxidant in the photochemical transformation of MCs. Our results indicate that singlet oxygen predominantly leads to degradation of the phycocyanin, pigments of blue green algae, hence reducing the degradation of MCs. The predominant process involves isomerization of the diene (6E to 6Z) in the Adda side chain via photosensitized isomerization involving the photoexcited phycocyanin. Our results indicate that photosensitized processes play a key role in the environmental fate and elimination of MCs in the natural waters. ^

Drug prescribing patterns in the General Medical Services Scheme in Ireland and projected costs to 2026

The primary objective is to investigate the main factors contributing to GMS expenditure on pharmaceutical prescribing and projecting this expenditure to 2026. This study is located in the area of pharmacoeconomic cost containment and projections literature. The thesis has five main aims: 1. To determine the main factors contributing to GMS expenditure on pharmaceutical prescribing. 2. To develop a model to project GMS prescribing expenditure in five year intervals to 2026, using 2006 Central Statistics Office (CSO) Census data and 2007 Health Service Executive{Primary Care Reimbursement Service (HSE{PCRS) sample data. 3. To develop a model to project GMS prescribing expenditure in five year intervals to 2026, using 2012 HSE{PCRS population data, incorporating cost containment measures, and 2011 CSO Census data. 4. To investigate the impact of demographic factors and the pharmacology of drugs (Anatomical Therapeutic Chemical (ATC)) on GMS expenditure. 5. To explore the consequences of GMS policy changes on prescribing expenditure and behaviour between 2008 and 2014. The thesis is centered around three published articles and is located between the end of a booming Irish economy in 2007, a recession from 2008{2013, to the beginning of a recovery in 2014. The literature identified a number of factors influencing pharmaceutical expenditure, including population growth, population aging, changes in drug utilisation and drug therapies, age, gender and location. The literature identified the methods previously used in predictive modelling and consequently, the Monte Carlo Simulation (MCS) model was used to simulate projected expenditures to 2026. Also, the literature guided the use of Ordinary Least Squares (OLS) regression in determining demographic and pharmacology factors influencing prescribing expenditure. The study commences against a backdrop of growing GMS prescribing costs, which has risen from e250 million in 1998 to over e1 billion by 2007. Using a sample 2007 HSE{PCRS prescribing data (n=192,000) and CSO population data from 2008, (Conway et al., 2014) estimated GMS prescribing expenditure could rise to e2 billion by2026. The cogency of these findings was impacted by the global economic crisis of 2008, which resulted in a sharp contraction in the Irish economy, mounting fiscal deficits resulting in Ireland's entry to a bailout programme. The sustainability of funding community drug schemes, such as the GMS, came under the spotlight of the EU, IMF, ECB (Trioka), who set stringent targets for reducing drug costs, as conditions of the bailout programme. Cost containment measures included: the introduction of income eligibility limits for GP visit cards and medical cards for those aged 70 and over, introduction of co{payments for prescription items, reductions in wholesale mark{up and pharmacy dispensing fees. Projections for GMS expenditure were reevaluated using 2012 HSE{PCRS prescribing population data and CSO population data based on Census 2011. Taking into account both cost containment measures and revised population predictions, GMS expenditure is estimated to increase by 64%, from e1.1 billion in 2016 to e1.8 billion by 2026, (ConwayLenihan and Woods, 2015). In the final paper, a cross{sectional study was carried out on HSE{PCRS population prescribing database (n=1.63 million claimants) to investigate the impact of demographic factors, and the pharmacology of the drugs, on GMS prescribing expenditure. Those aged over 75 (ẞ = 1:195) and cardiovascular prescribing (ẞ = 1:193) were the greatest contributors to annual GMS prescribing costs. Respiratory drugs (Montelukast) recorded the highest proportion and expenditure for GMS claimants under the age of 15. Drugs prescribed for the nervous system (Escitalopram, Olanzapine and Pregabalin) were highest for those between 16 and 64 years with cardiovascular drugs (Statins) were highest for those aged over 65. Females are more expensive than males and are prescribed more items across the four ATC groups, except among children under 11, (ConwayLenihan et al., 2016). This research indicates that growth in the proportion of the elderly claimants and associated levels of cardiovascular prescribing, particularly for statins, will present difficulties for Ireland in terms of cost containment. Whilst policies aimed at cost containment (co{payment charges, generic substitution, reference pricing, adjustments to GMS eligibility) can be used to curtail expenditure, health promotional programs and educational interventions should be given equal emphasis. Also policies intended to affect physicians prescribing behaviour include guidelines, information (about price and less expensive alternatives) and feedback, and the use of budgetary restrictions could yield savings.

Obstetric mode of delivery and child psychological development

Background/aims: Objective of the current thesis is to investigate the potential impact of birth by Caesarean section (CS) on child psychological development, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), behavioural difficulties and school performance. Structure/methods: Published literature to date on birth by CS, ASD and ADHD was reviewed (Chapter 2). Data from the UK Millennium Cohort Study (MCS) were analysed to determine the association between CS and ASD, ADHD and parent-reported behavioural difficulties (Chapter 3). The Swedish National Registers were used to further assess the association with ASD, ADHD and school performance (Chapters 4-6). Results: In the review, children born by CS were 23% more likely to be diagnosed with ASD after controlling for potential confounders. Only two studies reported adjusted estimates on the association between birth by CS and ADHD, results were conflicting and limited. CS was not associated with ASD, ADHD or behavioural difficulties in the UK MCS. In the Swedish National Registers, children born by CS were more likely to be diagnosed with ASD or ADHD. The association with elective CS did not persist when compared amongst siblings. There was little evidence of an association between birth by elective CS and poor school performance. Children born by elective CS had slight reduction in school performance. Conclusions: The lack of association with the elective CS in the sibling design studies indicates that the association in the population is most probably due to confounding. A small but significant association was found between birth by CS and school performance. However, the effect may have been due to residual confounding or confounding by indication and should be interpreted with caution. The overall conclusion is that birth by CS does not appear to have a causal relationship with the aspects of child psychological development investigated.

DJs, remixes e samples: inovação, memória e identidades na linguagem híbrida da música nas mídias

Dissertação apresentada ao Programa de Pós-Graduação em Comunicação da Universidade Municipal de São Caetano do Sul para a obtenção do título de Mestre em Comunicação

Mesenchymal chondrosarcoma: prognostic factors and outcome in 113 patients. A European Musculoskeletal Oncology Society study

BACKGROUND: Mesenchymal chondrosarcoma (MCS) is a distinct, very rare sarcoma with little evidence supporting treatment recommendations. PATIENTS AND METHODS: Specialist centres collaborated to report prognostic factors and outcome for 113 patients. RESULTS: Median age was 30 years (range: 11-80), male/female ratio 1.1. Primary sites were extremities (40%), trunk (47%) and head and neck (13%), 41 arising primarily in soft tissue. Seventeen patients had metastases at diagnosis. Mean follow-up was 14.9 years (range: 1-34), median overall survival (OS) 17 years (95% confidence interval (CI): 10.3-28.6). Ninety-five of 96 patients with localised disease underwent surgery, 54 additionally received combination chemotherapy. Sixty-five of 95 patients are alive and 45 progression-free (5 local recurrence, 34 distant metastases, 11 combined). Median progression-free survival (PFS) and OS were 7 (95% CI: 3.03-10.96) and 20 (95% CI: 12.63-27.36) years respectively. Chemotherapy administration in patients with localised disease was associated with reduced risk of recurrence (P=0.046; hazard ratio (HR)=0.482 95% CI: 0.213-0.996) and death (P=0.004; HR=0.445 95% CI: 0.256-0.774). Clear resection margins predicted less frequent local recurrence (2% versus 27%; P=0.002). Primary site and origin did not influence survival. The absence of metastases at diagnosis was associated with a significantly better outcome (P<0.0001). Data on radiotherapy indications, dose and fractionation were insufficiently complete, to allow comment of its impact on outcomes. Median OS for patients with metastases at presentation was 3 years (95% CI: 0-4.25). CONCLUSIONS: Prognosis in MCS varies considerably. Metastatic disease at diagnosis has the strongest impact on survival. Complete resection and adjuvant chemotherapy should be considered as standard of care for localised disease.

Deep Crustal Structure of the North-West African Margin from Combined Wide-angle and Reflection Seismic Data (MIRROR Seismic Survey)

The structure of the Moroccan and Nova Scotia conjugate rifted margins is of key importance for understanding the Mesozoic break-up and evolution of the northern central Atlantic Ocean basin. Seven combined multichannel reflection (MCS) and wide-angle seismic (OBS) data profiles were acquired along the Atlantic Moroccan margin between the latitudes of 31.5° and 33° N during the MIRROR seismic survey in 2011, in order to image the transition from continental to oceanic crust, to study the variation in crustal structure and to characterize the crust under the West African Coast Magnetic Anomaly (WACMA). The data were modeled using a forward modeling approach. The final models image crustal thinning from 36 km thickness below the continent to approximately 8 km in the oceanic domain. A 100 km wide zone characterized by rough basement topography and high seismic velocities up to 7.4 km/s in the lower crust is observed westward of the West African Coast Magnetic Anomaly. No basin underlain by continental crust has been imaged in this region, as has been identified north of our study area. Comparison to the conjugate Nova Scotian margin shows a similar continental crustal thickness and layer geometry, and the existence of exhumed and serpentinized upper mantle material on the Canadian side only. The oceanic crustal thickness is lower on the Canadian margin.