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Polycyclic aromatic hydrocarbons in fresh and cold-smoked Atlantic salmon fillets.
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Visciano P, Perugini M, Amorena M, Ianieri A
The occurrence of polycyclic aromatic hydrocarbons (PAHs) in smoked fish as a consequence of cold smoking was studied. Raw fillets of Salmo salar from Norway or the Irish Sea were sampled in a modern smokehouse and examined for PAH content. The same fillets, labeled with an identification number, were sampled immediately after the smoking process and analyzed. Among the investigated compounds, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, and benzo[ghi]perylene were detected in both raw and smoked fillets. No significant difference (P < 0.01) was observed between raw and smoked samples in the concentrations of six PAHs, but significant differences were found for fluorene, anthracene, fluoranthene, benz[a]anthracene, and benzo[ghi]perylene. Results confirm that PAHs concentrations in smoked fish are the product of both sea pollution and the smoking process. A modern smoking plant with an external smoke generator and a mild treatment as described here will not add significantly to the concentration of PAHs, except for some compounds.
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Complex precipitation pathways in multicomponent alloys.
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Clouet E, Laé L, Epicier T, Lefebvre W, Nastar M, Deschamps A
One usual way to strengthen a metal is to add alloying elements and to control the size and the density of the precipitates obtained. However, precipitation in multicomponent alloys can take complex pathways depending on the relative diffusivity of solute atoms and on the relative driving forces involved. In Al-Zr-Sc alloys, atomic simulations based on first-principle calculations combined with various complementary experimental approaches working at different scales reveal a strongly inhomogeneous structure of the precipitates: owing to the much faster diffusivity of Sc compared with Zr in the solid solution, and to the absence of Zr and Sc diffusion inside the precipitates, the precipitate core is mostly Sc-rich, whereas the external shell is Zr-rich. This explains previous observations of an enhanced nucleation rate in Al-Zr-Sc alloys compared with binary Al-Sc alloys, along with much higher resistance to Ostwald ripening, two features of the utmost importance in the field of light high-strength materials.
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Aldosterone antagonists: effective add-on therapy for the treatment of resistant hypertension.
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Gaddam KK, Pratt-Ubunama MN, Calhoun DA
Resistant hypertension is defined as blood pressure that remains above target levels despite treatment with three different antihypertensive agents. Cross-sectional analyses and hypertension outcome studies indicate that it is a common clinical problem, which will undoubtedly become increasingly prevelant with an aging and increasingly overwight population. Secondary causes of hypertension are common in patients with resistant hypertension, particularly hyperaldosteronism, with a prevalence of approximately 15-20%. This, however, is likely to be an underestimation of the role excess aldosterone plays in causing resistance to treatment. In subjects with resistant hypertension, suppressed renin levels are common, exceeding 60% in studies conducted by the authors and from centers elsewhere in the world, suggesting occurrence of excess aldosterone beyond cases of true primary aldosteronism. Recent clinical studies indicate that aldosterone antagonists provide significant additional blood pressure reduction when added to treatment regimens of patients with resistant hypertension independent of aldosterone levels. These agents are generally well tolerated. Hyperkalemia is an uncommon complication of aldosterone antagonists, but it can occur. Therefore, biochemical monitoring is necessary, particularly in high-risk patients.
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Functional Analysis of a Metal Response Element in the Regulatory Region of Flounder CYP 1A and Implications for Environmental Monitoring of Pollutants.
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Lewis NA, Williams TD, Chipman JK
Cytochrome P450 1A (CYP 1A) is a member of a multigene family of xenobiotic metabolizing enzymes. CYP 1A is highly inducible by numerous environmental contaminants including polycyclic aromatic hydrocarbons (PAHs), and is widely used in bio-monitoring studies. Therefore understanding the regulation of this gene is important for accurate interpretation of biomarker data. We describe here the functional role of a metal response element in the European flounder CYP 1A promoter region. To help elucidate the potential role of this MRE, reporter gene constructs with or without site-directed mutagenesis, were used in conjunction with a dual luciferase assay. The electrophoretic mobility shift assay (EMSA) was also used to investigate potential protein binding at this MRE site. Treatment with the prototypical PAH 3-methylcholanthrene (3MC) (1.0 microM) produced a dose-dependent response at the CYP 1A promoter, whereas treatment with cadmium (0 - 1.0 microM) produced little transcriptional activity at either the wild-type or mutated promoter. Co-treatment with cadmium (1.0 microM) and 3MC (1.0 microM) reduced induction at this promoter to 1.83 fold compared to 3MC treatment alone (4.0-fold induction). Mutation of the MRE site resulted in abolishment of this cadmium-related loss of 3MC-dependent activity. Furthermore, a retarded band was observed in the EMSA when the MRE was used as a probe and incubated with liver nuclear protein from flounder treated with cadmium. The results not only add to knowledge of the diversity in vertebrate CYP 1A regulation, but raise the complexity of interpretation of CYP 1A induction in monitoring studies that involve mixtures of PAH and metals.
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The need for neuroprotective therapies in Parkinson's disease: a clinical perspective.
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Poewe W
Slowing of disease progression remains a major unmet need in the treatment of Parkinson's disease (PD). Multiple factors are responsible for progression of disability in this disorder including worsening of cardinal motor features due to progressive nigral pathology, the evolution of poorly levodopa-responsive symptoms like freezing, postural instability and falls as well as motor complications of sustained treatment with levodopa. In addition, non-motor symptoms including cognitive decline, autonomic failure, sleep disorders and pain become increasingly prevalent with advancing disease and add to the overall burden of this disease. So far no treatment has been shown to significantly retard the progression of overall disability, and neuroprotective trials have been limited by design issues and a narrow focus on rates of decline of motor scores or imaging markers of nigrostriatal dysfunction only. Current evidence suggests that it may soon be possible to define populations at increased risk to develop PD and thus to target the "preclinical" phase of PD for neuroprotection. Such future trials will test intervention for their ability to prevent or retard the development of clinically overt PD in at-risk individuals.
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Attitudes and beliefs among patients treated with mood stabilizers.
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Kessing LV, Hansen HV, Bech P
ABSTRACT: BACKGROUND: There is increasing evidence that attitudes and beliefs are important in predicting adherence in depressive and bipolar disorders. However, such attitudes and beliefs on mood stabilizers have not been analysed by socio-demographic and clinical variables. METHODS: The Mood Stabilizer Compliance Questionnaire (MSQC) was mailed to a large population of patients with depressive or bipolar disorder representative of patients treated at their first contacts to hospital settings in Denmark. RESULTS: Of the 1005 recipients, 49.9 % responded to the letter and among these 256 indicated that they previously had been or currently were in treatment with a mood stabilizer. A large proportion of the patients (40 to 80 %) had non-correct views on the effect of mood stabilizers. Older patients consistently had a more negative view on the doctor-patient relationship, more non-correct views on the effect of mood stabilizers and a more negative view on mood stabilizers. There was no difference in the attitudes and beliefs according to the type of disorder (depressive or bipolar), the number of psychiatric hospitalisations or according to the type of the current doctor (general practitioner, private psychiatrist, community psychiatry doctor, hospital doctor, other doctor). CONCLUSION: There is a need of improving knowledge and attitudes toward diagnosis and treatment especially among elder patients as this may add to improve the prognosis of depressive and bipolar disorders.
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Psychopathology in Females with Attention-Deficit/Hyperactivity Disorder: A Controlled, Five-Year Prospective Study.
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Biederman J, Monuteaux MC, Mick E, Spencer T, Wilens TE, Klein KL, Price JE, Faraone SV
BACKGROUND: Despite the importance of understanding the long-term outcome of children with attention-deficit/hyperactivity disorder (ADHD), the available literature is predominantly based on male samples. This study estimated the lifetime burden of comorbid psychopathology in a large sample of girls with and without ADHD followed up over five years. METHODS: We conducted a blind, five-year prospective longitudinal study of girls with (n=140) and without (n=122) ADHD, aged 6-18 years at baseline, consecutively ascertained from either community pediatricians or psychiatrists at an academic medical center. At the five-year follow-up, 123 (88%) and 112 (92%) of the ADHD and control children, respectively, were re-assessed at a mean age of 16.7 years. Psychiatric disorders were assessed using blinded structured diagnostic interviews. RESULTS: At follow-up, females with ADHD were at significantly higher risk than controls to manifest disruptive behavior, mood and anxiety disorders, and substance dependence. The magnitude of increased risk was greatest for major depression and oppositional-defiant disorder, followed by substance dependence and anxiety disorders. CONCLUSIONS: These prospective follow-up findings documenting high morbidity associated with ADHD extend to females previously reported findings in male samples and underscore the importance of early recognition and intervention efforts for youth with ADHD of both genders.
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Effect of lamotrigine on cognition in children with epilepsy.
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Pressler RM, Binnie CD, Coleshill SG, Chorley GA, Robinson RO
BACKGROUND: Lamotrigine does not affect cognition in healthy adult volunteers or adult patients with epilepsy, but its effect on cognition in children is uncertain. OBJECTIVE: To compare the effect of lamotrigine and placebo on cognition in children with well-controlled or mild epilepsy. METHOD: In a double-blind, placebo-controlled, crossover study, 61 children with well-controlled or mild epilepsy were randomly assigned to add-on therapy with either lamotrigine followed by placebo or placebo followed by lamotrigine. Each treatment phase was 9 weeks, the crossover period 5 weeks. A neuropsychological test battery was performed during EEG monitoring at baseline and at the end of placebo and drug phases. The paired Student' t test was used for statistical analysis for neuropsychological data (two tailed) with a p value of 0.01 considered significant. Carryover and period effect were analyzed with generalized linear modeling (SPSS 10). RESULTS: Forty-eight children completed the study. Seizure frequency was similar during both treatment phases. No significant difference was found in continuous performance, binary choice reaction time, verbal and nonverbal recognition, computerized visual searching task, verbal and spatial delayed recognition, and verbal and nonverbal working memory between placebo and lamotrigine treatment phase. There was no significant carryover and period effect when corrected for randomization. CONCLUSION: Lamotrigine exhibits no clinically significant cognitive effects in adjunctive therapy for children with epilepsy.
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Colour perception in ADHD.
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Banaschewski T, Ruppert S, Tannock R, Albrecht B, Becker A, Uebel H, Sergeant JA, Rothenberger A
Attention-deficit/hyperactivity disorder (ADHD) is associated with unexplained impairments on speeded naming of coloured stimuli. These deficits may reflect hypofunctioning retinal dopaminergic mechanisms impairing particularly blue-yellow colour discrimination. Colour perception and rapid colour naming ability were investigated in 14 children with ADHD and 13 healthy peers matched for age, gender, and IQ, using the Farnsworth-Munsell 100 Hue Test (FMT) and the Stroop-Colour-Word test. Children with ADHD committed more errors on the FMT, particularly on discrimination of colours along the blue-yellow axis, and were slower on Stroop subtests involving colour naming. However, the latter deficit was accounted for similarly by blue-yellow and red-green discrimination abilities. Blue-yellow colour perception problems in ADHD contribute to but do not fully explain the observed slowed colour naming.
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Semaphorin 7A Is a Negative Regulator of T Cell Responses.
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Czopik AK, Bynoe MS, Palm N, Raine CS, Medzhitov R
Semaphorins play an essential role in axonal guidance, and emerging evidence points to diverse functions of several Semaphorin family members in the immune system. Semaphorin 7A (Sema7A) promotes axonal growth in the central nervous system. Here, we show that Sema7A also plays a critical role in negative regulation of T cell activation and function. T cells deficient in Sema7A exhibit enhanced homeostatic and antigen-induced proliferative response. Moreover, autoreactive Sema7A-deficient T cells mediate aggressive autoimmune disease. The deficiency in Sema7A leads to defective TCR downmodulation and T cell hyperresponsiveness. These results demonstrate an important role of Sema7A in limiting autoimmune responses and add to growing evidence of shared signaling pathways used by the immune and nervous systems.
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Effects of quetiapine on the brain-derived neurotrophic factor expression in the hippocampus and neocortex of rats.
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Park SW, Lee SK, Kim JM, Yoon JS, Kim YH
The effects of antipsychotics on the brain-derived neurotrophic factor (BDNF) expression have been controversial. This study aimed to investigate the effects of chronic quetiapine administration on the BDNF mRNA expression in hippocampus and neocortex of rats with or without immobilization stress. The chronic administration (21 days) of quetiapine (10mg/kg) significantly attenuated the decreased BDNF mRNA expression in the both hippocampal and cortical regions of rats caused by immobilization stress, and significantly increased the BDNF mRNA expression in the dentate gyrus of rats even without the immobilization stress. These results could add some theoretical bases to explain why quetiapine may improve cognitive symptoms of schizophrenia by stimulating BDNF mRNA expression.
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Treatment with leuprolide acetate and hormonal add-back for up to 10 years in stage IV endometriosis patients with chronic pelvic pain.
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Bedaiwy MA, Casper RF
This pilot study examined the effect of a low-dose E and pulsed progestogen hormone therapy (HT) regimen for add-back during long-term GnRH-agonist therapy on bone mineral density (BMD) in five patients with stage IV endometriosis. Bone mineral density was stable after initiation of HT for the entire follow-up period (up to 10 years). One patient stopped her treatment on two occasions to conceive and was successful each time with delivery of a normal baby. No patient had return of pelvic pain after HT add-back.
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Spatial and seasonal variations in the water quality of the Amu Darya River (Central Asia).
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Crosa G, Froebrich J, Nikolayenko V, Stefani F, Galli P, Calamari D
Although the use of the water resources in Uzbekistan is strongly limited by their quality, it has to be noted that there is a lack of information and data within the international scientific literature with regard to the water chemical characteristics of the Amu Darya River, one of the main water resources in Central Asia. To add to such knowledge, this paper examines the spatial and temporal variation of the water quality of the Amu Darya River in order to assess its degree of degradation and the main causal factors. The functional relationships of the pollutants with respect to the flow regime are investigated. Finally an "opportune temporal window" for water withdrawal for filling the reservoirs, in relation to human consumption, will be indicated. The high salinization levels of the waters are mainly due to the presence of sulphates and chlorine. At the up-stream site salinity, although presenting elevated concentrations, does not exceed palatability levels; after the 450km point the opportune temporal window for water withdrawal with acceptable salinity values is reduced to the period from May to September. Two main driving forces govern the temporal variation of the salinity of the Amu Darya water: a low drainage density of the area which limits the salt loads induced by the natural runoff processes, and snow and glacier melting in the upper catchment area which promotes dilution of the dissolved salts during the high-flow period. During low-flow periods salinity is strongly influenced by the return of waters used for land washing and irrigation.
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A study of the kid-kINDL questionnaire scores for children with developmental disorders in normal classes and their parents
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Furusho J, Kubagawa T, Satoh H, Shibata R, Nemoto Y, Matsuzaki K, Sone M, Watanabe S
The KINDL-questionnaire is able to measure degrees of health and adaptability in relation to quality of life (QOL) in children. The questionnaire can be completed by children, adolescents, and their parents (parent-version). We had translated Kid-KINDL questionnaire into Japanese as Questionnaire for Measuring QOL in Japanese Elementary School Children, and reported their reliability and validity. This study investigates Japanese elementary school version of the Kid-KINDL questionnaire scores consisting of 6 dimensions (4 items each;total score, 100) for children with developmental disorders without mental retardation including high-functioned pervasive developmental disorder, attention deficit/hyperactivity disorder and learning disorder, and the parent-version scores for their mothers. Twenty individuals in normal class and their mothers participated after informed consents were obtained. Their total QOL scores were significantly lower than those in control group. Four of 6 dimensions consisting of emotional well-being, self-esteem, family, friends and school had significantly lower points. Their mothers' points in total QOL scores and all dimensions except for family dimension were significantly lower than those in control group. In comparison of scores between children with mild developmental disorders and their mothers, children estimated lower in self-esteem and family dimensions instead mother estimated lower in health, emotional well-being and school dimensions. There was no difference in total scores between them. Children with mild developmental disorders and their mothers estimate lower points of QOL scores than those of the normal control group. There are different perceptions in 5 of 6 dimensions between the children and their mothers.
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A narrative account of the impact of positive thinking on discussions about death and dying.
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McGrath C, Montgomery K, White K, Kerridge IH
GOALS OF WORK: The purpose of this study was to explore the experience of autologous stem cell transplant recipients (ASCT) and those who care for them. MATERIALS AND METHODS: This was a qualitative prospective, longitudinal study. Ten patients who were about to have ASCT and nine carers were recruited to the study. Interviews were to be conducted at regular intervals six times over 2 years. The narratives of two widowed carers were analysed using Grounded Theory and read for themes on positive thinking and death. MAIN RESULTS: Positive thinking has a range of meanings, and its use can have a range of consequences. It can either be a useful coping strategy or can interfere with important conversations and planning about the end of life, and subsequently add to the distress of a grieving partner. CONCLUSIONS: It is important for patients, their partners and their health professionals to be able to discuss potential adverse consequences of illness, including death, without being hindered by the obligation to be positive or optimistic.
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Activation in Ventral Prefrontal Cortex is Sensitive to Genetic Vulnerability for Attention-Deficit Hyperactivity Disorder.
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Durston S, Mulder M, Casey BJ, Ziermans T, van Engeland H
BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a heritable neuropsychiatric disorder, associated with atypical patterns of brain activation in functional imaging studies. Neuroimaging measures may serve as an intermediate phenotype in genetic studies of ADHD, as they are putatively more closely linked to gene expression than a clinical diagnosis. METHODS: We used rapid, mixed-trial, event-related functional magnetic resonance imaging (fMRI) to investigate changes in brain activation during a go no-go task in boys with ADHD, their unaffected siblings, and matched control subjects. RESULTS: On the hardest inhibitory trials in our task, children and adolescents with ADHD had lower accuracy than control subjects, whereas their unaffected siblings did not. Control subjects activated a network of regions, including ventral prefrontal and inferior parietal cortex. Both children and adolescents with ADHD and their unaffected siblings showed decreased activation in these areas, as well as fewer correlations between performance and activation. CONCLUSIONS: These findings suggest that the magnitude of activation during successful inhibitions is sensitive to genetic vulnerability for ADHD in a number of regions, including ventral prefrontal cortex. If this can be replicated in future studies, this suggests that neuroimaging measures related to inhibitory control may be suitable as intermediate phenotypes in studies investigating gene effects in ADHD.
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Diarrhoea-causing agents in children aged less than five in Tunja, Colombia
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Manrique-Abril FG, Tigne y Diane B, Bello SE, Ospina JM
OBJECTIVES: Determining the prevalence and type of infectious ADD-causing agents in a sample of children aged less than five who consulted the IPS in Tunja during 2004. MATERIAL AND METHODS: A cross-sectional study was designed. Data was obtained by surveying 129 children younger than 5 suffering from ADD. Samples of faeces were obtained following outpatient consultation at San Rafael Hospital and SaludCoop's clinic in Tunja. RESULTS: Rotavirus was found in 48.1% of cases, Shigella in 0.8%, E. coli in 13.9%, Campylobacter in 2.3%, Giardia lamblia in 12.4% and E. hitolytica in 7%. The causative agent could not be identified in 15.5% of cases. The statistical association grew with age for Rotavirus (p < 0.01), E. coli (p < 0.05) and campylobacter (p < 0.001). CONCLUSION: Rotavirus is the major causative agent of ADD in children younger than one year and, generally, in children aged less than five. The prevalence found was similar to data reported in studies carried out in Facatatativá, Bogotá, Santander, Manizales and the Chocó in Colombia and studies carried out in Venezuela, Peru and Mexico.
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Predictors of healthcare outcomes and costs related to medication use in patients with acne in the United States.
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Balkrishnan R, Kulkarni AS, Cayce K, Feldman SR
This study investigated the relationship among health status, costs linked with the treatment of acne in the United States, and other aspects related to medication use. The US Medical Expenditure Panel Survey (MEPS) database was analyzed for a cohort of people with acne. This cross-sectional study obtained costs, demographics, healthcare service utilization, and clinical patient variables from the MEPS database. The EuroQol Group's EQ-5D scores available in MEPS were used for health status information. Multivariate weighted analysis was performed for data for approximately 5 million patients (weighted sample size). Nearly 70% of the patients used some type of medication for acne. Acne-related medication accounted for approximately 36% of the total acne-related annual healthcare costs, with an average of 2 annual acne prescription refills per patient. Increased number of refills of acne-related medications was associated with an improvement in health status (P<.05). Increased physician office-based visits were the only predictors of higher acne-related annual healthcare costs (P<.01). Adherence to acne medications is an important component of better health status. Pharmacologic treatment of acne does not significantly add to acne-related annual healthcare costs.
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Building statistical models to analyze species distributions.
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Latimer AM, Wu S, Gelfand AE, Silander JA
Models of the geographic distributions of species have wide application in ecology. But the nonspatial, single-level, regression models that ecologists have often employed do not deal with problems of irregular sampling intensity or spatial dependence, and do not adequately quantify uncertainty. We show here how to build statistical models that can handle these features of spatial prediction and provide richer, more powerful inference about species niche relations, distributions, and the effects of human disturbance. We begin with a familiar generalized linear model and build in additional features, including spatial random effects and hierarchical levels. Since these models are fully specified statistical models, we show that it is possible to add complexity without sacrificing interpretability. This step-by-step approach, together with attached code that implements a simple, spatially explicit, regression model, is structured to facilitate self-teaching. All models are developed in a Bayesian framework. We assess the performance of the models by using them to predict the distributions of two plant species (Proteaceae) from South Africa's Cape Floristic Region. We demonstrate that making distribution models spatially explicit can be essential for accurately characterizing the environmental response of species, predicting their probability of occurrence, and assessing uncertainty in the model results. Adding hierarchical levels to the models has further advantages in allowing human transformation of the landscape to be taken into account, as well as additional features of the sampling process.
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Plasma glutathione peroxidase activity as a potential indicator of hypoxic stress in breath-hold diving.
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Rousseau AS, Richer C, Richard MJ, Favier A, Margaritis I
INTRODUCTION: Diving mammals can cope with oxidants which are produced in excess during the reoxygenation of hypoxic tissues. This study addresses the question of whether antioxidants can adapt and whether it allows humans to tolerate the hypoxic stress induced by a single breath-holding in the course of a dynamic diving exercise and protect them from oxidative insult. METHODS: There were 20 male subjects who performed submaximal apnea dynamic diving (ADD). Nine control subjects stayed out of the water and breathed normally. Venous blood samples were collected 1 h before and immediatly after ADD. RESULTS: ADD induced a significant increase in plasma glutathione peroxidase (GPx-3) activity (from 397.5 +/- 44.4 to 410 +/- 43 U x L(-1)), blood reduced glutathione (GSH) (from 1060 +/- 302 to 1292 +/- 213 micromol x L(-1)), and in plasma creatine kinase activity (from 215 +/- 137 to 235 +/- 152 U x L(-1)). The activity of the erythrocyte superoxide dismutase and glutathione peroxidase, as well as the blood oxidized glutathione and the plasma thiobarbituric acid reactive substances concentrations, were maintained at their basal level. The level of training, characterized by the duration and distance of the dive, had no effect on the markers used. CONCLUSION: GPx-3 and GSH could constitute the most readily mobilizable antioxidants that would then contribute to the buffering against a sudden increase in the generation of radical oxygen species. These biomarkers could be used as tools for establishing oxidative stress during hypoxia. The response of GPx-3 to hypoxia could be of physiological relevance.
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