Experimental model of intervertebral disc degeneration by needle puncture in Wistar rats

Animal models of intervertebral disc degeneration play an important role in clarifying the physiopathological mechanisms and testing novel therapeutic strategies. The objective of the present study is to describe a simple animal model of disc degeneration involving Wistar rats to be used for research studies. Disc degeneration was confirmed and classified by radiography, magnetic resonance and histological evaluation. Adult male Wistar rats were anesthetized and submitted to percutaneous disc puncture with a 20-gauge needle on levels 6-7 and 8-9 of the coccygeal vertebrae. The needle was inserted into the discs guided by fluoroscopy and its tip was positioned crossing the nucleus pulposus up to the contralateral annulus fibrosus, rotated 360° twice, and held for 30 s. To grade the severity of intervertebral disc degeneration, we measured the intervertebral disc height from radiographic images 7 and 30 days after the injury, and the signal intensity T2-weighted magnetic resonance imaging. Histological analysis was performed with hematoxylin-eosin and collagen fiber orientation using picrosirius red staining and polarized light microscopy. Imaging and histological score analyses revealed significant disc degeneration both 7 and 30 days after the lesion, without deaths or systemic complications. Interobserver histological evaluation showed significant agreement. There was a significant positive correlation between histological score and intervertebral disc height 7 and 30 days after the lesion. We conclude that the tail disc puncture method using Wistar rats is a simple, cost-effective and reproducible model for inducing disc degeneration.

An improved experimental model for peripheral neuropathy in rats

A modification of the Bennett and Xie chronic constriction injury model of peripheral painful neuropathy was developed in rats. Under tribromoethanol anesthesia, a single ligature with 100% cotton glace thread was placed around the right sciatic nerve proximal to its trifurcation. The change in the hind paw reflex threshold after mechanical stimulation observed with this modified model was compared to the change in threshold observed in rats subjected to the Bennett and Xie or the Kim and Chung spinal ligation models. The mechanical threshold was measured with an automated electronic von Frey apparatus 0, 2, 7, and 14 days after surgery, and this threshold was compared to that measured in sham rats. All injury models produced significant hyperalgesia in the operated hind limb. The modified model produced mean ± SD thresholds in g (19.98 ± 3.08, 14.98 ± 1.86, and 13.80 ± 1.00 at 2, 7, and 14 days after surgery, respectively) similar to those obtained with the spinal ligation model (20.03 ± 1.99, 13.46 ± 2.55, and 12.46 ± 2.38 at 2, 7, and 14 days after surgery, respectively), but less variable when compared to the Bennett and Xie model (21.20 ± 8.06, 18.61 ± 7.69, and 18.76 ± 6.46 at 2, 7, and 14 days after surgery, respectively). The modified method required less surgical skill than the spinal nerve ligation model.

Early detection of metabolic and energy disorders by thermal time series stochastic complexity analysis

Maintenance of thermal homeostasis in rats fed a high-fat diet (HFD) is associated with changes in their thermal balance. The thermodynamic relationship between heat dissipation and energy storage is altered by the ingestion of high-energy diet content. Observation of thermal registers of core temperature behavior, in humans and rodents, permits identification of some characteristics of time series, such as autoreference and stationarity that fit adequately to a stochastic analysis. To identify this change, we used, for the first time, a stochastic autoregressive model, the concepts of which match those associated with physiological systems involved and applied in male HFD rats compared with their appropriate standard food intake age-matched male controls (n=7 per group). By analyzing a recorded temperature time series, we were able to identify when thermal homeostasis would be affected by a new diet. The autoregressive time series model (AR model) was used to predict the occurrence of thermal homeostasis, and this model proved to be very effective in distinguishing such a physiological disorder. Thus, we infer from the results of our study that maximum entropy distribution as a means for stochastic characterization of temperature time series registers may be established as an important and early tool to aid in the diagnosis and prevention of metabolic diseases due to their ability to detect small variations in thermal profile.

Plasma levels and placental expression of vaspin in pregnant women with diabetes mellitus

The present study aimed to investigate visceral adipose tissue-specific serpin (vaspin) concentrations in serum and term placentas and relate these values to insulin resistance and lipid parameters in women with gestational diabetes mellitus (GDM). A total of 30 GDM subjects and 27 age-matched pregnant women with normal glucose tolerance (NGT, control) were included. Serum glucose, glycated hemoglobin (HbA1c), lipid profile, insulin, and vaspin were measured at the end of pregnancy, and homeostasis model of assessment-insulin resistance (HOMA-IR) values were calculated. Vaspin mRNA and protein levels in placentas were measured by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting, respectively. Serum vaspin levels were significantly lower in the GDM group than in controls (0.49±0.24 vs 0.83±0.27 ng/mL, respectively; P<0.01). Three days after delivery, serum vaspin levels were significantly decreased in subjects with GDM (0.36±0.13 vs0.49±0.24 ng/mL, P<0.01). However, in the GDM group, serum vaspin levels were not correlated with the parameters evaluated. In contrast, in the control group, serum vaspin levels were positively correlated with triglycerides (TG; r=0.45, P=0.02) and very low-density lipoprotein cholesterol (VLDL-C; r=0.42, P=0.03). Placental mRNA vaspin (0.60±0.32 vs0.68±0.32, P=0.46) and protein (0.30±0.08 vs0.39±0.26; P=0.33) levels in the GDM group did not differ significantly from those in the control group, but were negatively correlated with neonatal birth weight in the GDM group (r=-0.48, P=0.03; r=-0.88; P<0.01). Our findings indicated that vaspin may be an important adipokine involved in carbohydrate and lipid metabolism and may also play a role in fetal development.

IGF2, LEPR, POMC, PPARG, and PPARGC1 gene variants are associated with obesity-related risk phenotypes in Brazilian children and adolescents

Association studies of genetic variants and obesity and/or obesity-related risk factors have yielded contradictory results. The aim of the present study was to determine the possible association of five single-nucleotide polymorphisms (SNPs) located in the IGF2, LEPR, POMC, PPARG, and PPARGC1genes with obesity or obesity-related risk phenotypes. This case-control study assessed overweight (n=192) and normal-weight (n=211) children and adolescents. The SNPs were analyzed using minisequencing assays, and variables and genotype distributions between the groups were compared using one-way analysis of variance and Pearson's chi-square or Fisher's exact tests. Logistic regression analysis adjusted for age and gender was used to calculate the odds ratios (ORs) for selected phenotype risks in each group. No difference in SNP distribution was observed between groups. In children, POMC rs28932472(C) was associated with lower diastolic blood pressure (P=0.001), higher low-density lipoprotein (LDL) cholesterol (P=0.014), and higher risk in overweight children of altered total cholesterol (OR=7.35, P=0.006). In adolescents, IGF2 rs680(A) was associated with higher glucose (P=0.012) and higher risk in overweight adolescents for altered insulin (OR=10.08, P=0.005) and homeostasis model of insulin resistance (HOMA-IR) (OR=6.34, P=0.010). PPARGrs1801282(G) conferred a higher risk of altered insulin (OR=12.31, P=0.003), and HOMA-IR (OR=7.47, P=0.005) in overweight adolescents. PARGC1 rs8192678(A) was associated with higher triacylglycerols (P=0.005), and LEPR rs1137101(A) was marginally associated with higher LDL cholesterol (P=0.017). LEPR rs1137101(A) conferred higher risk for altered insulin, and HOMA-IR in overweight adolescents. The associations observed in this population suggested increased risk for cardiovascular diseases and/or type 2 diabetes later in life for individuals carrying these alleles.

Effect of air-temperature and diet composition on the drying process of pellets for japanese abalone (Haliotis discus hannai) feeding

The aim of this research was to study the effect of air-temperature and diet composition on the mass transfer kinetics during the drying process of pellets used for Japanese Abalone (Haliotis discus hannai) feeding. In the experimental design, three temperatures were used for convective drying, as well as three different diet compositions (Diets A, B and C), in which the amount of fishmeal, spirulin, algae, fish oil and cornstarch varied. The water diffusion coefficient of the pellets was determined using the equation of Fick's second law, which resulted in values between 0.84-1.94×10-10 m²/s. The drying kinetics was modeled using Page, Modified Page, Root of time, Exponential, Logarithmic, Two-Terms, Modified Henderson-Pabis and Weibull models. In addition, two new models, referred to as 'Proposed' models 1 and 2, were used to simulate this process. According to the statistical tests applied, the models that best fitted the experimental data were Modified Henderson-Pabis, Weibull and Proposed model 2, respectively. Bifactorial analysis of variance ANOVA showed that Diet A (fishmeal 44%, spirulin 9%, fish oil 1% and cornstarch 36%) presented the highest diffusion coefficient values, which were favored by the temperature increase in the drying process.

Climate change and global responsibility - the role of energy consumption, GDP and CO2 emissions

Climate change is one of the biggest challenges faced by this generation. Despite being the single most important environmental challenge facing the planet and despite over two decades of international climate negotiations, global greenhouse gas (GHG) emissions continue to rise. By the middle of this century, GHGs must be reduced by as much as 40-70% if dangerous climate change is to be avoided. In the Kyoto Protocol no quantitative emission limitation and reduction commitments were placed on the developing countries. For the planning of the future commitments period and possible participation of developing countries, information of the functioning of the energy systems, CO2 emissions development in different sectors, energy use and technological development in developing countries is essential. In addition to the per capita emissions, the efficiency of the energy system in relation to GHG emissions is crucial for the decision of future long-term burden sharing between countries. Country’s future development of CO2 emissions can be defined by the estimated CO2 intensity of the future and the estimated GDP growth. The changes in CO2 intensity depend on several factors, but generally developed countries’ intensity has been increasing in the industrialization phase and decreasing when their economy shifts more towards the system dominated by the service sector. The level of the CO2 intensity depends by a large extent on the production structure and the energy sources that are used. Currently one of the most urgent issues regarding global climate change is to decide the future of the Kyoto Protocol. Negotiations on this topic have already been initiated, with the aim of being finalised by the 2015. This thesis provides insights into the various approaches that can be used to characterise the concept of comparable efforts for developing countries in a future international climate agreement. The thesis examines the post-Kyoto burden sharing questions for developing countries using the contraction and convergence model, which is one approach that has been proposed to allocate commitments regarding future GHG emissions mitigation. This new approach is a practical tool for the evaluation of the Kyoto climate policy process and global climate change negotiations from the perspective of the developing countries.

Motives and barriers for engaging in collaborative consumption in Finland

In this thesis the consumers’ expected motives and barriers for engaging in collaborative consumption in Finland are studied. The phenomenon is observed through the lens of consumer theory and it is connected to the context using Hofstede’s 6-D model. The phenomenon is new and there are almost no recorded results in the background research, and when considering the limitations of this study, there are no results at all. Therefore, combining different kinds of literature, as well as taking along consumer theory and Hofstede’s model that explains cultural factors, it was possible to compile a comprehensive general view of the present state of the phenomenon. The actual study was conducted using qualitative methods and the solution was sought collecting data from six in-depth interviews with interviewees having experience from using, or offering resources, or both. According to the results, the primary motive in all modes of consumption was economic. Anti-materialism, anti-consumption, and expanding lifestyle were another a bit more general motives. Perceived barriers were, especially as a new result, the amount of trouble one has to see and in single modes, a lack of trust, the used platform and too expensive prices.

Analytical modelling of bacterial migration and accumulation with rate-limited sorption in discrete fractures

An analytical model for bacterial accumulation in a discrete fractllre has been developed. The transport and accumlllation processes incorporate into the model include advection, dispersion, rate-limited adsorption, rate-limited desorption, irreversible adsorption, attachment, detachment, growth and first order decay botl1 in sorbed and aqueous phases. An analytical solution in Laplace space is derived and nlln1erically inverted. The model is implemented in the code BIOFRAC vvhich is written in Fortran 99. The model is derived for two phases, Phase I, where adsorption-desorption are dominant, and Phase II, where attachment-detachment are dominant. Phase I ends yvhen enollgh bacteria to fully cover the substratllm have accllillulated. The model for Phase I vvas verified by comparing to the Ogata-Banks solution and the model for Phase II was verified by comparing to a nonHomogenous version of the Ogata-Banks solution. After verification, a sensitiv"ity analysis on the inpllt parameters was performed. The sensitivity analysis was condllcted by varying one inpllt parameter vvhile all others were fixed and observing the impact on the shape of the clirve describing bacterial concentration verSllS time. Increasing fracture apertllre allovvs more transport and thus more accllffilliation, "Vvhich diminishes the dllration of Phase I. The larger the bacteria size, the faster the sllbstratum will be covered. Increasing adsorption rate, was observed to increase the dllration of Phase I. Contrary to the aSSllmption ofllniform biofilm thickness, the accllffilliation starts frOll1 the inlet, and the bacterial concentration in aqlleous phase moving towards the olitiet declines, sloyving the accumulation at the outlet. Increasing the desorption rate, redllces the dliration of Phase I, speeding IIp the accllmlilation. It was also observed that Phase II is of longer duration than Phase I. Increasing the attachment rate lengthens the accliffililation period. High rates of detachment speeds up the transport. The grovvth and decay rates have no significant effect on transport, althollgh increases the concentrations in both aqueous and sorbed phases are observed. Irreversible adsorption can stop accllillulation completely if the vallIes are high.

Age-related changes in ERPs associated with context-based and response-based interference

Age-related differences in information processing have often been explained through deficits in older adults' ability to ignore irrelevant stimuli and suppress inappropriate responses through inhibitory control processes. Functional imaging work on young adults by Nelson and colleagues (2003) has indicated that inferior frontal and anterior cingulate cortex playa key role in resolving interference effects during a delay-to-match memory task. Specifically, inferior frontal cortex appeared to be recruited under conditions of context interference while the anterior cingulate was associated with interference resolution at the stage of response selection. Related work has shown that specific neural activities related to interference resolution are not preserved in older adults, supporting the notion of age-related declines in inhibitory control (Jonides et aI., 2000, West et aI., 2004b). In this study the time course and nature of these inhibition-related processes were investigated in young and old adults using high-density ERPs collected during a modified Sternberg task. Participants were presented with four target letters followed by a probe that either did or did not match one of the target letters held in working memory. Inhibitory processes were evoked by manipulating the nature of cognitive conflict in a particular trial. Conflict in working memory was elicited through the presentation of a probe letter in immediately previous target sets. Response-based conflict was produced by presenting a negative probe that had just been viewed as a positive probe on the previous trial. Younger adults displayed a larger orienting response (P3a and P3b) to positive probes relative to a non-target baseline. Older adults produced the orienting P3a and 3 P3b waveforms but their responses did not differentiate between target and non-target stimuli. This age-related change in response to targetness is discussed in terms of "early selection/late correction" models of cognitive ageing. Younger adults also showed a sensitivity in their N450 response to different levels of interference. Source analysis of the N450 responses to the conflict trials of younger adults indicated an initial dipole in inferior frontal cortex and a subsequent dipole in anterior cingulate cortex, suggesting that inferior prefrontal regions may recruit the anterior cingulate to exert cognitive control functions. Individual older adults did show some evidence of an N450 response to conflict; however, this response was attenuated by a co-occurring positive deflection in the N450 time window. It is suggested that this positivity may reflect a form of compensatory activity in older adults to adapt to their decline in inhibitory control.

Richard Nelson Bell - Iris Sloman Wedding Day Photo, 1939

A black and white photograph taken in 1939 on the occasion of the marriage of Richard Nelson Bell to Iris Sloman. Pictured in the photograph, from left to right, are: Bert Sloman; Richard Nelson Bell; Iris Sloman Bell; and Helen Beatty Sloman. This photograph was in the possession of Rick Bell, the son of Richard Nelson and Iris Bell. The Bell - Sloman family descends from former Black slaves from the United States.Bert Sloman (Albert Edward Sloman) passed away in 1986 at Kitchener-Waterloo, Ontario. His wife Vera Matilda Sloman passed away January 4, 2011 at Cambridge Memorial Hospital. They had a son, Ron Sloman.

Network Similarity Measures and Automatic Construction of Graph Models using Genetic Programming

A complex network is an abstract representation of an intricate system of interrelated elements where the patterns of connection hold significant meaning. One particular complex network is a social network whereby the vertices represent people and edges denote their daily interactions. Understanding social network dynamics can be vital to the mitigation of disease spread as these networks model the interactions, and thus avenues of spread, between individuals. To better understand complex networks, algorithms which generate graphs exhibiting observed properties of real-world networks, known as graph models, are often constructed. While various efforts to aid with the construction of graph models have been proposed using statistical and probabilistic methods, genetic programming (GP) has only recently been considered. However, determining that a graph model of a complex network accurately describes the target network(s) is not a trivial task as the graph models are often stochastic in nature and the notion of similarity is dependent upon the expected behavior of the network. This thesis examines a number of well-known network properties to determine which measures best allowed networks generated by different graph models, and thus the models themselves, to be distinguished. A proposed meta-analysis procedure was used to demonstrate how these network measures interact when used together as classifiers to determine network, and thus model, (dis)similarity. The analytical results form the basis of the fitness evaluation for a GP system used to automatically construct graph models for complex networks. The GP-based automatic inference system was used to reproduce existing, well-known graph models as well as a real-world network. Results indicated that the automatically inferred models exemplified functional similarity when compared to their respective target networks. This approach also showed promise when used to infer a model for a mammalian brain network.

Statistical Inference for Computable General Equilibrium Models with Application to a Model of the Moroccan Economy

We study the problem of measuring the uncertainty of CGE (or RBC)-type model simulations associated with parameter uncertainty. We describe two approaches for building confidence sets on model endogenous variables. The first one uses a standard Wald-type statistic. The second approach assumes that a confidence set (sampling or Bayesian) is available for the free parameters, from which confidence sets are derived by a projection technique. The latter has two advantages: first, confidence set validity is not affected by model nonlinearities; second, we can easily build simultaneous confidence intervals for an unlimited number of variables. We study conditions under which these confidence sets take the form of intervals and show they can be implemented using standard methods for solving CGE models. We present an application to a CGE model of the Moroccan economy to study the effects of policy-induced increases of transfers from Moroccan expatriates.

Contribution of tachykinin and kinin receptors in central autonomic control of blood pressure and behavioural activity in hypertensive rats

This work aims at studing the role of tachykinin NK-3 receptor (R) and kinin B1R in central autonomic regulation of blood pressure (BP) and to determine whether the B1R is overexpressed and functional in rat models of hypertension by measuring the effect of a B1R agonist on behavioural activity. Assumptions: (1) NK-3R located in the ventral tegmental area (VTA) modulates the mesolimbic dopaminergic system and has a tonic activity in hypertension; (2) B1R is overexpressed in the brain of hypertensive rats and has a tonic activity, which contributes to hypertension via a dopamine mechanism; (3) the inhibition of NK-3R and B1R with selective antagonists, reduces central dopaminergic hyperactivity and reverses hypertension. A model of genetic hypertension and a model of experimental hypertension were used: spontaneously hypertensive rats (SHR, 16 weeks) and Wistar-Kyoto (WKY) rats infused for 14 days with angiotensin II (Ang II) (200 ng / kg / min, subcutaneous (s.c.) with Alzet mini pump). The age-matched untreated WKY rats served as common controls. In the first study (article # 1), the cardiovascular response in SHR was evaluated following intracebroventricular (i.c.v.) and/or intra-VTA injection of an agonist (senktide) and antagonists (SB222200 and R-820) of NK-3R. These responses have also been characterized using selective dopamine antagonists DA-D1R (SCH23390), DA-D2R (raclopride) or non-selective dopamine DA-D2R (haloperidol). Also the VTA has been destroyed by ibotenic acid. The pressor response induced by senktide and the anti-hypertensive response induced by SB222200 or R-820 were more pronounced by intra-VTA. These responses were prevented by pre-treatment with raclopride and haloperidol. The lesion of the VTA has prevented the pressor response relayed by senktide (i.c.v.) and the anti-hypertensive effect of R-820 (i.c.v.). In addition, SB222200 (intra-VTA) prevented the pressor response of senktide (i.c.v.) and conversely, senktide (i.c.v.) prevented the antihypertensive effect of SB222200 (intra-VTA). The second study (article # 2) showed that the B1R antagonist (SSR240612) administered by gavage or i.c.v. reverses hypertension in both models. This anti-hypertensive effect was prevented by raclopride and haloperidol. In contrast, the two B1R antagonists (R-715 and R-954) injected s.c., which do not cross the blood-brain barrier reduced weakly blood pressure in hypertensive rats. In the third study (article # 3), the i.c.v. injection of a selective kinin B1R agonist Sar[DPhe8][des-Arg9]BK caused behavioural responses in SHR and Ang II-treated rats and had no effect in control WKY rats . The responses elicited by B1R agonist were blocked by an antagonist of NK-1 (RP67580), an antagonist of NMDA glutamate receptor (DL-AP5), an inhibitor of nitric oxide synthase (NOS) (L -NNA) as well as raclopride and SCH23390.The responses were modestly affected by the inhibitor of inducible NOS (iNOS). The B1R mRNA (measured by RT-PCR) was significantly increased in the hypothalamus, the VTA and the nucleus accumbens of hypertensive animals (SHR and treated with Ang II) compared with control rats. These neuropharmacological studies suggest that: (1) the NK-3R from the VTA is involved in the maintenance of hypertension in SHR by increasing DA transmission in the midbrain; (2) the B1R in SHR and Ang II-treated rats contributes to hypertension via a central mechanism involving DA-D2R; (3) the central B1R increases locomotor activity and nocifensive behaviours via the release of substance P (NK-1), DA and nitric oxide in both rat models of hypertension. Thus, the brain tachykinin NK-3R and kinin B1R represent potential therapeutic targets for the treatment of hypertension. The modulation of the mesolimbic/mesocortical dopaminergic pathway by these receptors suggests their involvement in other physiological functions (pleasure, motor activity, coordination of the response to stress) and pathophysiology (anxiety, depression).

The relationship between product design and business models in the context of sustainability

Dans les sphères du développement durable, des modèles d’affaires et du design de produit, certains leviers rendent le croisement de ces trois sphères de plus en plus pertinent. Au croisement de ces trois sphères se trouve une opportunité de comprendre les relations existantes entre le design de produit et les modèles d’affaires afin d’aider les décideurs à développer des solutions davantage durables. L’approche méthodologique de cette recherche utilise un système complexe et est basée sur un paradigme pragmatique. En vue de répondre à la question « Dans quelle mesure des modèles d’affaires et le design de produit sont liés dans un contexte de développement durable? », cette recherche a soigneusement analysé trois cas: Better Place, une compagnie californienne ayant développé une infrastructure permettant le chargement des voitures électriques; Interface Inc., un manufacturier mondial de tuiles de tapis commerciales établi à Atlanta; et Métacycle, un concept d’entreprise développé par une équipe de chercheurs en design à Montréal. Chaque cas a été analysé en corrélant des aspects du design de produit à des éléments de leur modèle d’affaires. Les résultats montrent que dans le contexte du développement durable, le design de produit et les modèles d’affaires sont interdépendants. Les résultats peuvent être résumés en six points: il existe des relations applicables universellement; les innovations de design substantielles jouent un rôle important dans le développement durable; la « durabilité » peut être une qualité émergente d’un modèle d’affaires; les partenariats peuvent être vitaux pour l’intégration des systèmes; un modèle de services a des bénéfices et des limitations considérables; le design peut agir comme levier à l’utilisation d’énergies renouvelables. Pratiquer simultanément l’innovation du modèle d’affaires et du produit peut apporter une valeur ajoutée, susciter des opportunités et augmenter l’efficience sur plusieurs facettes. Toutefois, les risques et les coûts de tels procédés sont souvent très élevés. En aidant à comprendre et définir comment les trois sphères mentionnées plus tôt sont interdépendantes, cette recherche pourrait idéalement inspirer des recherches supplémentaires sur le sujet. L’application par des organisations de la méthodologie et des apprentissages résultant de cette recherche peut permettre à d’autres d’utiliser le croisement entre l’innovation de produit et l’innovation du modèle d’affaires afin de résoudre des enjeux sociaux et environnementaux complexes.