Trazodone increases arousal threshold in obstructive sleep apnoea.

A low arousal threshold is believed to predispose to breathing instability during sleep. The present authors hypothesised that trazodone, a nonmyorelaxant sleep-promoting agent, would increase the effort-related arousal threshold in obstructive sleep apnoea (OSA) patients. In total, nine OSA patients, mean+/-sd age 49+/-9 yrs, apnoea/hypopnoea index 52+/-32 events.h(-1), were studied on 2 nights, one with trazodone at 100 mg and one with a placebo, in a double blind randomised fashion. While receiving continuous positive airway pressure (CPAP), repeated arousals were induced: 1) by increasing inspired CO(2) and 2) by stepwise decreases in CPAP level. Respiratory effort was measured with an oesophageal balloon. End-tidal CO(2 )tension (P(ET,CO(2))) was monitored with a nasal catheter. During trazodone nights, compared with placebo nights, the arousals occurred at a higher P(ET,CO(2)) level (mean+/-sd 7.30+/-0.57 versus 6.62+/-0.64 kPa (54.9+/-4.3 versus 49.8+/-4.8 mmHg), respectively). When arousals were triggered by increasing inspired CO(2) level, the maximal oesophageal pressure swing was greater (19.4+/-4.0 versus 13.1+/-4.9 cm H(2)O) and the oesophageal pressure nadir before the arousals was lower (-5.1+/-4.7 versus -0.38+/-4.2 cm H(2)O) with trazodone. When arousals were induced by stepwise CPAP drops, the maximal oesophageal pressure swings before the arousals did not differ. Trazodone at 100 mg increased the effort-related arousal threshold in response to hypercapnia in obstructive sleep apnoea patients and allowed them to tolerate higher CO(2) levels.

Decision Support Methods for Global Optomization

Immobile location-allocation (LA) problems is a type of LA problem that consists in determining the service each facility should offer in order to optimize some criterion (like the global demand), given the positions of the facilities and the customers. Due to the complexity of the problem, i.e. it is a combinatorial problem (where is the number of possible services and the number of facilities) with a non-convex search space with several sub-optimums, traditional methods cannot be applied directly to optimize this problem. Thus we proposed the use of clustering analysis to convert the initial problem into several smaller sub-problems. By this way, we presented and analyzed the suitability of some clustering methods to partition the commented LA problem. Then we explored the use of some metaheuristic techniques such as genetic algorithms, simulated annealing or cuckoo search in order to solve the sub-problems after the clustering analysis

Endometriosis: alternative methods of medical treatment.

Endometriosis is an inflammatory estrogen-dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The main purpose of endometriosis management is alleviating pain associated to the disease. This can be achieved surgically or medically, although in most women a combination of both treatments is required. Long-term medical treatment is usually needed in most women. Unfortunately, in most cases, pain symptoms recur between 6 months and 12 months once treatment is stopped. The authors conducted a literature search for English original articles, related to new medical treatments of endometriosis in humans, including articles published in PubMed, Medline, and the Cochrane Library. Keywords included "endometriosis" matched with "medical treatment", "new treatment", "GnRH antagonists", "Aromatase inhibitors", "selective progesterone receptor modulators", "anti-TNF α", and "anti-angiogenic factors". Hormonal treatments currently available are effective in the relief of pain associated to endometriosis. Among new hormonal drugs, association to aromatase inhibitors could be effective in the treatment of women who do not respond to conventional therapies. GnRH antagonists are expected to be as effective as GnRH agonists, but with easier administration (oral). There is a need to find effective treatments that do not block the ovarian function. For this purpose, antiangiogenic factors could be important components of endometriosis therapy in the future. Upcoming researches and controlled clinical trials should focus on these drugs.

Advances in Sequence Analysis: Theory, Methods, Applications

This book gives a general view of sequence analysis, the statistical study of successions of states or events. It includes innovative contributions on life course studies, transitions into and out of employment, contemporaneous and historical careers, and political trajectories. The approach presented in this book is now central to the life-course perspective and the study of social processes more generally. This volume promotes the dialogue between approaches to sequence analysis that developed separately, within traditions contrasted in space and disciplines. It includes the latest developments in sequential concepts, coding, atypical datasets and time patterns, optimal matching and alternative algorithms, survey optimization, and visualization. Field studies include original sequential material related to parenting in 19th-century Belgium, higher education and work in Finland and Italy, family formation before and after German reunification, French Jews persecuted in occupied France, long-term trends in electoral participation, and regime democratization. Overall the book reassesses the classical uses of sequences and it promotes new ways of collecting, formatting, representing and processing them. The introduction provides basic sequential concepts and tools, as well as a history of the method. Chapters are presented in a way that is both accessible to the beginner and informative to the expert.

Genetic redox dysregulation induces behavioural deficits in the adult mouse: an animal model for schizophrenia

Background: Glutathione (GSH), a major cellular redox regulator and antioxidant, is decreased in cerebrospinal fluid and prefrontal cortex of schizophrenia patients. The gene of the key GSH-synthesizing enzyme, glutamate-cysteine ligase, modifier (GCLM) subunit, is associated with schizophrenia, suggesting that the deficit in the GSH system is of genetic origin. Using the GCLM knock-out (KO) mouse as model system with 60% decreased brain GSH levels and, thus, strong vulnerability to oxidative stress, we have shown that GSH dysregulation results in abnormal mouse brain morphology (e.g., reduced parvalbumin, PV, immuno-reactivity in frontal areas) and function. Additional oxidative stress, induced by GBR12909 (a dopamine re-uptake inhibitor), enhances morphological changes even further. Aim: In the present study we use the GCLM KO mouse model system, asking now, whether GSH dysregulation also compromises mouse behaviour and cognition. Methods: Male and female wildtype (WT) and GCLM-KO mice are treated with GBR12909 or phosphate buffered saline (PBS) from postnatal day (P) 5 to 10, and are behaviourally tested at P 60 and older. Results: In comparison to WT, KO animals of both sexes are hyperactive in the open field, display more frequent open arm entries on the elevated plus maze, longer float latencies in the Porsolt swim test, and more frequent contacts of novel and familiar objects. Contrary to other reports of animal models with reduced PV immuno-reactivity, GCLM-KO mice display normal rule learning capacity and perform normally on a spatial recognition task. GCLM-KO mice do, however, show a strong deficit in object-recognition after a 15 minutes retention delay. GBR12909 treatment exerts no additional effect. Conclusions: The results suggest that animals with impaired regulation of brain oxidative stress are impulsive and have reduced behavioural control in novel, unpredictable contexts. Moreover, GSH dysregulation seems to induce a selective attentional or stimulus-encoding deficit: despite intensive object exploration, GCLM-KO mice cannot discriminate between novel and familiar objects. In conclusion, the present data indicate that GSH dysregulation may contribute to the manifestation of behavioural and cognitive anomalies that are associated with schizophrenia.

Postmortem angiography: review of former and current methods.

OBJECTIVE: Postmortem investigations are becoming more and more sophisticated. CT and MRI are already being used in pathology and forensic medicine. In this context, the impact of postmortem angiography increases because of the rapid evaluation of organ-specific vascular patterns, vascular alteration under pathologic and physiologic conditions, and tissue changes induced by artificial and unnatural causes. CONCLUSION: In this article, the advantages and disadvantages of former and current techniques and contrast agents are reviewed.

Genes for normal sleep and sleep disorders.

Sleep and wakefulness are complex behaviors that are influenced by many genetic and environmental factors, which are beginning to be discovered. The contribution of genetic components to sleep disorders is also increasingly recognized as important. Point mutations in the prion protein, period 2, and the prepro-hypocretin/orexin gene have been found as the cause of a few sleep disorders but the possibility that other gene defects may contribute to the pathophysiology of major sleep disorders is worth in-depth investigations. However, single gene disorders are rare and most common disorders are complex in terms of their genetic susceptibility, environmental effects, gene-gene, and gene-environment interactions. We review here the current progress in the genetics of normal and pathological sleep.

Free-living energy expenditure assessed by two different methods in rural Gambian men.

OBJECTIVE: To assess total free-living energy expenditure (EE) in Gambian farmers with two independent methods, and to determine the most realistic free-living EE and physical activity in order to establish energy requirements for rural populations in developing countries. DESIGN: In this cross-sectional study two methods were applied at the same time. SETTING: Three rural villages and Dunn Nutrition Centre Keneba, MRC, The Gambia. SUBJECTS: Eight healthy, male subjects were recruited from three rural Gambian villages in the sub-Sahelian area (age: 25 +/- 4y; weight: 61.2 +/- 10.1 kg; height: 169.5 +/- 6.5 cm, body mass index: 21.2 +/- 2.5 kg/m2). INTERVENTION: We assessed free-living EE with two inconspicuous and independent methods: the first one used doubly labeled water (DLW) (2H2 18O) over a period of 12 days, whereas the second one was based on continuous heart rate (HR) measurements on two to three days using individual regression lines (HR vs EE) established by indirect calorimetry in a respiration chamber. Isotopic dilution of deuterium (2H2O) was also used to assess total body water and hence fat-free mass (FFM). RESULTS: EE assessed by DLW was found to be 3880 +/- 994 kcal/day (16.2 +/- 4.2 MJ/day). Expressed per unit body weight the EE averaged 64.2 +/- 9.3 kcal/kg/d (269 +/- 38 kJ/kg/d). These results were consistent with the EE results assessed by HR: 3847 +/- 605 kcal/d (16.1 +/- 2.5 MJ/d) or 63.4 +/- 8.2 kcal/kg/d (265 +/- 34kJ/kg/d). Physical activity index, expressed as a multiple of basal metabolic rate (BMR), averaged 2.40 +/- 0.41 (DLW) or 2.40 +/- 0.28 (HR). CONCLUSIONS: These findings suggest an extremely high level of physical activity in Gambian men during intense agricultural work (wet season). This contrasts with the relative food shortage, previously reported during the harvesting period. We conclude that the assessment of EE during the agricultural season in non-industrialized countries needs further investigations in order to obtain information on the energy requirement of these populations. For this purpose the use of the DLW and HR methods have been shown to be useful and complementary.

Implementing statistical learning methods through Bayesian networks (Part 2): bayesian evaluations for results of black toner analyses in forensic document examination

This paper presents and discusses the use of Bayesian procedures - introduced through the use of Bayesian networks in Part I of this series of papers - for 'learning' probabilities from data. The discussion will relate to a set of real data on characteristics of black toners commonly used in printing and copying devices. Particular attention is drawn to the incorporation of the proposed procedures as an integral part in probabilistic inference schemes (notably in the form of Bayesian networks) that are intended to address uncertainties related to particular propositions of interest (e.g., whether or not a sample originates from a particular source). The conceptual tenets of the proposed methodologies are presented along with aspects of their practical implementation using currently available Bayesian network software.

Portafolio selection with skewness: a comparison of methods and a generalized two fund separation result

This contribution compares existing and newly developed techniques for geometrically representing mean-variances-kewness portfolio frontiers based on the rather widely adapted methodology of polynomial goal programming (PGP) on the one hand and the more recent approach based on the shortage function on the other hand. Moreover, we explain the working of these different methodologies in detail and provide graphical illustrations. Inspired by these illustrations, we prove a generalization of the well-known two fund separation theorem from traditionalmean-variance portfolio theory.

Kernel-based methods for change detection in remote sensing images

Nowadays, the joint exploitation of images acquired daily by remote sensing instruments and of images available from archives allows a detailed monitoring of the transitions occurring at the surface of the Earth. These modifications of the land cover generate spectral discrepancies that can be detected via the analysis of remote sensing images. Independently from the origin of the images and of type of surface change, a correct processing of such data implies the adoption of flexible, robust and possibly nonlinear method, to correctly account for the complex statistical relationships characterizing the pixels of the images. This Thesis deals with the development and the application of advanced statistical methods for multi-temporal optical remote sensing image processing tasks. Three different families of machine learning models have been explored and fundamental solutions for change detection problems are provided. In the first part, change detection with user supervision has been considered. In a first application, a nonlinear classifier has been applied with the intent of precisely delineating flooded regions from a pair of images. In a second case study, the spatial context of each pixel has been injected into another nonlinear classifier to obtain a precise mapping of new urban structures. In both cases, the user provides the classifier with examples of what he believes has changed or not. In the second part, a completely automatic and unsupervised method for precise binary detection of changes has been proposed. The technique allows a very accurate mapping without any user intervention, resulting particularly useful when readiness and reaction times of the system are a crucial constraint. In the third, the problem of statistical distributions shifting between acquisitions is studied. Two approaches to transform the couple of bi-temporal images and reduce their differences unrelated to changes in land cover are studied. The methods align the distributions of the images, so that the pixel-wise comparison could be carried out with higher accuracy. Furthermore, the second method can deal with images from different sensors, no matter the dimensionality of the data nor the spectral information content. This opens the doors to possible solutions for a crucial problem in the field: detecting changes when the images have been acquired by two different sensors.

Evaluation of four whole-plant inoculation methods to analyze the pathogenicity of Erwinia amylovora under quarantine conditions

Four methods were tested to assess the fire-blight disease response on grafted pear plants. The leaves of the plants were inoculated with Erwinia amylovora suspensions by pricking with clamps, cutting with scissors, local infiltration, and painting a bacterial suspension onto the leaves with a paintbrush. The effects of the inoculation methods were studied in dose-time-response experiments carried out in climate chambers under quarantine conditions. A modified Gompertz model was used to analyze the disease-time relatiobbnships and provided information on the rate of infection progression (rg) and time delay to the start of symptoms (t0). The disease-pathogen-dose relationships were analyzed according to a hyperbolic saturation model in which the median effective dose (ED50) of the pathogen and maximum disease level (ymax) were determined. Localized infiltration into the leaf mesophile resulted in the early (short t0) but slow (low rg) development of infection whereas in leaves pricked with clamps disease symptoms developed late (long t0) but rapidly (high rg). Paintbrush inoculation of the plants resulted in an incubation period of medium length, a moderate rate of infection progression, and low ymax values. In leaves inoculated with scissors, fire-blight symptoms developed early (short t0) and rapidly (high rg), and with the lowest ED50 and the highest ymax

Body composition: overview of methods and future directions of research.

A short overview is given on the most important analytical body composition methods. Principles of the methods and advantages and limitations of the methods are discussed also in relation to other fields of research such as energy metabolism. Attention is given to some new developments in body composition research such as chemical multiple-compartment models, computerized tomography or nuclear magnetic resonance imaging (tissue level), and multifrequency bioelectrical impedance. Possible future directions of body composition research in the light of these new developments are discussed.

A comparative analysis of two methods for the calculation of electric-field-induced perturbations to molecular vibration

Two common methods of accounting for electric-field-induced perturbations to molecular vibration are analyzed and compared. The first method is based on a perturbation-theoretic treatment and the second on a finite-field treatment. The relationship between the two, which is not immediately apparent, is made by developing an algebraic formalism for the latter. Some of the higher-order terms in this development are documented here for the first time. As well as considering vibrational dipole polarizabilities and hyperpolarizabilities, we also make mention of the vibrational Stark effec

A comparative analysis by means of quantum molecular similarity measures of density distributions derived from conventional ab initio and density functional methods

A procedure based on quantum molecular similarity measures (QMSM) has been used to compare electron densities obtained from conventional ab initio and density functional methodologies at their respective optimized geometries. This method has been applied to a series of small molecules which have experimentally known properties and molecular bonds of diverse degrees of ionicity and covalency. Results show that in most cases the electron densities obtained from density functional methodologies are of a similar quality than post-Hartree-Fock generalized densities. For molecules where Hartree-Fock methodology yields erroneous results, the density functional methodology is shown to yield usually more accurate densities than those provided by the second order Møller-Plesset perturbation theory