A Novel Preclinical Model for Chronic Thrombo-Embolic Pulmonary Hypertension development, validation and characterization

Since the disease chronic thrombo-embolic pulmonary hypertension (CTEPH), which is caused by an abnormal increase in blood pressure in the lungs due to obstructions, is still incompletely understood, therapeutic interventions are limited, and a curative medicine is still not available for CTEPH, we aim to unravel some mechanisms of this disease in this dissertation. To establish this, we developed a large animal model for CTEPH in which chronic catheters in and around the heart enable serial and awake measurements of blood pressures, cardiac output and oxygen metabolism both at rest and during exercise. The research in this thesis provides an insight in some of the underlying mechanisms which cause remodeling of the pulmonary vasculature and the heart in this disease. Our results indicate that specific research in global signaling pathways such as the vasodilator nitric oxide, the vasoconstrictor endothelin and Rho-kinase are very important for the development of more effective CTEPH treatment. In addition, we show the importance of exercise testing in PH, especially in the early stages to provide earlier diagnosis. All together we provided a lot of information on the pathophysiology of CTEPH with the help of a novel large animal model. Although we gathered all this information, future studies need to be conducted before the ideal, curative therapy will reach the patient

Analytic Hierarchy Process in Group Decision Making: Much Ado About Nothing

This paper examines the use of the Analytic Hierarchy Process (AHP) in individual and group decision making. Group AHP without individual AHP resulted in the exchange of the most common information while the combination of both group and individual AHP resulted in the least. The use of AHP in group decision making took longer, but did not result in better decisions. Subjects reported that they processed less information when using AHP and felt there was less credibility in the information discussed

A blinded, randomized, controlled trial assessing conservative management strategies for frozen shoulder

BACKGROUND: There is little evidence for the optimal form of nonoperative treatment in the management of frozen shoulder. This study assesses the efficacy of current physiotherapy strategies. METHODS: All primary care referrals of frozen shoulder to our physiotherapy department were included during a 12-month period. Of these referrals, 17% met the inclusion criteria for primary idiopathic frozen shoulder. The 75 patients were randomly assigned to 1 of 3 groups: group exercise class, individual physiotherapy, and home exercises alone. A single independent physiotherapist, who was blinded to the treatment groups, made all assessments. Range of motion, Constant score, Oxford Shoulder Score, Short Form 36, and Hospital Anxiety and Disability Scale (HADS) outcome measures were performed at baseline, 6 weeks, 6 months, and 1 year. RESULTS: The exercise class group improved from a mean Constant score of 39.8 at baseline to 71.4 at 6 weeks and 88.1 at 1 year. There was a significant improvement in shoulder symptoms on Oxford and Constant scores (P < .001). This improvement was greater than with individual physiotherapy or home exercises alone (P < .001). The improvement in range of motion was significantly greater in both physiotherapy groups over home exercises (P < .001). HADS scores significantly improved during the course of treatment (P < .001). The improvement in HADS anxiety score was significantly greater in both physiotherapy intervention groups than in home exercises alone. CONCLUSIONS: A hospital-based exercise class can produce a rapid recovery from a frozen shoulder with a minimum number of visits to the hospital and is more effective than individual physiotherapy or a home exercise program

Evaluating signatures of glacial refugia for North Atlantic benthic marine taxa

A goal of phylogeography is to relate patterns of genetic differentiation to potential historical geographic isolating events. Quaternary glaciations, particularly the one culminating in the Last Glacial Maximum ;21 ka (thousands of years ago), greatly affected the distributions and population sizes of temperate marine species as their ranges retreated southward to escape ice sheets. Traditional genetic models of glacial refugia and routes of recolonization include these predictions: low genetic diversity in formerly glaciated areas, with a small number of alleles/ haplotypes dominating disproportionately large areas, and high diversity including ‘‘private’’ alleles in glacial refugia. In the Northern Hemisphere, low diversity in the north and high diversity in the south are expected. This simple model does not account for the possibility of populations surviving in relatively small northern periglacial refugia. If these periglacial populations experienced extreme bottlenecks, they could have the low genetic diversity expected in recolonized areas with no refugia, but should have more endemic diversity (private alleles) than recently recolonized areas. This review examines evidence of putative glacial refugia for eight benthic marine taxa in the temperate North Atlantic. All data sets were reanalyzed to allow direct comparisons between geographic patterns of genetic diversity and distribution of particular clades and haplotypes including private alleles. We contend that for marine organisms the genetic signatures of northern periglacial and southern refugia can be distinguished from one another. There is evidence for several periglacial refugia in northern latitudes, giving credence to recent climatic reconstructions with less extensive glaciation

Resting-State Functional Connectivity and Network Analysis of Cerebellum with Respect to Crystallized IQ and Gender

During the last years, it has been established that the prefrontal and posterior parietal brain lobes, which are mostly related to intelligence, have many connections to cerebellum. However, there is a limited research investigating cerebellum's relationship with cognitive processes. In this study, the network of cerebellum was analyzed in order to investigate its overall organization in individuals with low and high crystallized Intelligence Quotient (IQ). Functional magnetic resonance imaging (fMRI) data were selected from 136 subjects in resting-state from the Human Connectome Project (HCP) database and were further separated into two IQ groups composed of 69 low-IQ and 67 high-IQ subjects. Cerebellum was parcellated into 28 lobules/ROIs (per subject) using a standard cerebellum anatomical atlas. Thereafter, correlation matrices were constructed by computing Pearson's correlation coefficients between the average BOLD time-series for each pair of ROIs inside the cerebellum. By computing conventional graph metrics, small-world network properties were verified using the weighted clustering coefficient and the characteristic path length for estimating the trade-off between segregation and integration. In addition, a connectivity metric was computed for extracting the average cost per network. The concept of the Minimum Spanning Tree (MST) was adopted and implemented in order to avoid methodological biases in graph comparisons and retain only the strongest connections per network. Subsequently, six global and three local metrics were calculated in order to retrieve useful features concerning the characteristics of each MST. Moreover, the local metrics of degree and betweenness centrality were used to detect hubs, i.e., nodes with high importance. The computed set of metrics gave rise to extensive statistical analysis in order to examine differences between low and high-IQ groups, as well as between all possible gender-based group combinations. Our results reveal that both male and female networks have small-world properties with differences in females (especially in higher IQ females) indicative of higher neural efficiency in cerebellum. There is a trend toward the same direction in men, but without significant differences. Finally, three lobules showed maximum correlation with the median response time in low-IQ individuals, implying that there is an increased effort dedicated locally by this population in cognitive tasks

Reorganization of functional connectivity as a correlate of cognitive recovery in acquired brain injury.

Cognitive processes require a functional interaction between specialized multiple, local and remote brain regions. Although these interactions can be strongly altered by an acquired brain injury, brain plasticity allows network reorganization to be principally responsible for recovery. The present work evaluates the impact of brain injury on functional connectivity patterns. Networks were calculated from resting-state magnetoencephalographic recordings from 15 brain injured patients and 14 healthy controls by means of wavelet coherence in standard frequency bands. We compared the parameters defining the network, such as number and strength of interactions as well as their topology, in controls and patients for two conditions: following a traumatic brain injury and after a rehabilitation treatment. A loss of delta- and theta-based connectivity and conversely an increase in alpha- and beta-band-based connectivity were found. Furthermore, connectivity parameters approached controls in all frequency bands, especially in slow-wave bands. A correlation between network reorganization and cognitive recovery was found: the reduction of delta-band-based connections and the increment of those based on alpha band correlated with Verbal Fluency scores, as well as Perceptual Organization and Working Memory Indexes, respectively. Additionally, changes in connectivity values based on theta and beta bands correlated with the Patient Competency Rating Scale. The current study provides new evidence of the neurophysiological mechanisms underlying neuronal plasticity processes after brain injury, and suggests that these changes are related with observed changes at the behavioural leve

The Brain Matures with Stronger Functional Connectivity and Decreased Randomness of Its Network

We investigated the development of the brain's functional connectivity throughout the life span (ages 5 through 71 years) by measuring EEG activity in a large population-based sample. Connectivity was established with Synchronization Likelihood. Relative randomness of the connectivity patterns was established with Watts and Strogatz' (1998) graph parameters C (local clustering) and L (global path length) for alpha (∼10 Hz), beta (∼20 Hz), and theta (∼4 Hz) oscillation networks. From childhood to adolescence large increases in connectivity in alpha, theta and beta frequency bands were found that continued at a slower pace into adulthood (peaking at ∼50 yrs). Connectivity changes were accompanied by increases in L and C reflecting decreases in network randomness or increased order (peak levels reached at ∼18 yrs). Older age (55+) was associated with weakened connectivity. Semi-automatically segmented T1 weighted MRI images of 104 young adults revealed that connectivity was significantly correlated to cerebral white matter volume (alpha oscillations: r = 33, p<01; theta: r = 22, p<05), while path length was related to both white matter (alpha: max. r = 38, p<001) and gray matter (alpha: max. r = 36, p<001; theta: max. r = 36, p<001) volumes. In conclusion, EEG connectivity and graph theoretical network analysis may be used to trace structural and functional development of the brain