Showing papers by "Laval University published in 2004"
TL;DR: This comprehensive review summarizes the current status in phosphorus-removal technologies from the most common approaches, like metal precipitation, constructed wetland systems, adsorption by various microorganisms either in a free state or immobilized in polysaccharide gels, to enhanced biological phosphorus removal using activated sludge systems, and several innovative engineering solutions.
1,324 citations
TL;DR: In this article, the authors examined the relationship between audit committee characteristics and the extent of corporate earnings management as measured by the level of income-increasing and income-decreasing abnormal accruals and found that aggressive earnings management is negatively associated with the financial and governance expertise of audit committee members, with indicators of independence, and with the presence of a clear mandate defining the responsibilities of the committee.
Abstract: This study investigates whether the expertise, independence, and activities of a firm's audit committee have an effect on the quality of its publicly released financial information. In particular, we examine the relationship between audit committee characteristics and the extent of corporate earnings management as measured by the level of income‐increasing and income‐decreasing abnormal accruals. Using two groups of U.S. firms, one with relatively high and one with relatively low levels of abnormal accruals in the year 1996, we find a significant association between earnings management and audit committee governance practices. We find that aggressive earnings management is negatively associated with the financial and governance expertise of audit committee members, with indicators of independence, and with the presence of a clear mandate defining the responsibilities of the committee. The association is similar for both income‐increasing and income‐decreasing earnings management, suggesting that audit com...
1,285 citations
TL;DR: Evidence of significantly high levels of molecular divergence among eight growth QTL where two of the strongest candidate loci under the influence of directional selection exhibited parallel reductions of gene flow over multiple populations is found.
Abstract: As natural selection must act on underlying genetic variation, discovering the number and location of loci under the influence of selection is imperative towards understanding adaptive divergence in evolving populations. Studies employing genome scans have hypothesized that the action of divergent selection should reduce gene flow at the genomic locations implicated in adaptation and speciation among natural populations, yet once ‘outlier’ patterns of variation have been identified the function and role of such loci needs to be confirmed. We integrated adaptive QTL mapping and genomic scans among diverging sympatric pairs of the lake whitefish (Coregonus clupeaformis) species complex in order to test the hypothesis that differentiation between dwarf and normal ecotypes at growth-associated QTL was maintained by directional selection. We found evidence of significantly high levels of molecular divergence among eight growth QTL where two of the strongest candidate loci under the influence of directional selection exhibited parallel reductions of gene flow over multiple populations.
1,074 citations
TL;DR: In this paper, the authors identify the trajectories of physical aggression during early childhood and, second, identify antecedents of high-level physical aggression early in life and identify targets for preventive interventions.
Abstract: Objectives. Physical aggression in children is a major public health problem. Not only is childhood physical aggression a precursor of the physical and mental health problems that will be visited on victims, but also aggressive children themselves are at higher risk of alcohol and drug abuse, accidents, violent crimes, depression, suicide attempts, spouse abuse, and neglectful and abusive parenting. Furthermore, violence commonly results in serious injuries to the perpetrators themselves. Although it is unusual for young children to harm seriously the targets of their physical aggression, studies of physical aggression during infancy indicate that by 17 months of age, the large majority of children are physically aggressive toward siblings, peers, and adults. This study aimed, first, to identify the trajectories of physical aggression during early childhood and, second, to identify antecedents of high levels of physical aggression early in life. Such antecedents could help to understand better the developmental origins of violence later in life and to identify targets for preventive interventions. Methods. A random population sample of 572 families with a 5-month-old newborn was recruited. Assessments of physical aggression frequency were obtained from mothers at 17, 30, and 42 months after birth. Using a semiparametric, mixture model, distinct clusters of physical aggression trajectories were identified. Multivariate logit regression analysis was then used to identify which family and child characteristics, before 5 months of age, predict individuals on a high-level physical aggression trajectory from 17 to 42 months after birth. Results. Three trajectories of physical aggression were identified. The first was composed of children who displayed little or no physical aggression. These individuals were estimated to account for ∼28% of the sample. The largest group, estimated at ∼58% of the sample, followed a rising trajectory of modest aggression. Finally, a group, estimated to comprise ∼14% of the sample, followed a rising trajectory of high physical aggression. Best predictors before or at birth of the high physical aggression trajectory group, controlling for the levels of the other risk factors, were having young siblings (odds ratio [OR]: 4.00; confidence interval [CI]: 2.2–7.4), mothers with high levels of antisocial behavior before the end of high school (OR: 3.1; CI: 1.1–8.6), mothers who started having children early (OR: 3.1; CI: 1.4–6.8), families with low income (OR: 2.6; CI: 1.3–5.2), and mothers who smoked during pregnancy (OR: 2.2; CI: 1.1–4.1). Best predictors at 5 months of age were mothers’ coercive parenting behavior (OR: 2.3; CI: 1.1–4.7) and family dysfunction (OR: 2.2; CI: 1.2–4.1). The OR for a high-aggression trajectory was 10.9 for children whose mother reported both high levels of antisocial behavior and early childbearing. Conclusions. Most children have initiated the use of physical aggression during infancy, and most will learn to use alternatives in the following years before they enter primary school. Humans seem to learn to regulate the use of physical aggression during the preschool years. Those who do not, seem to be at highest risk of serious violent behavior during adolescence and adulthood. Results from the present study indicate that children who are at highest risk of not learning to regulate physical aggression in early childhood have mothers with a history of antisocial behavior during their school years, mothers who start childbearing early and who smoke during pregnancy, and parents who have low income and have serious problems living together. All of these variables are relatively easy to measure during pregnancy. Preventive interventions should target families with high-risk profiles on these variables. Experiments with such programs have shown long-term impacts on child abuse and child antisocial behavior. However, these impacts were not observed in families with physical violence. The problem may be that the prevention programs that were provided did not specifically target the parents’ control over their physical aggression and their skills in teaching their infant not to be physically aggressive. Most intervention programs to prevent youth physical aggression have targeted school-age children. If children normally learn not to be physically aggressive during the preschool years, then one would expect that interventions that target infants who are at high risk of chronic physical aggression would have more of an impact than interventions 5 to 10 years later, when physical aggression has become a way of life.
926 citations
TL;DR: The lack of standardized operational research diagnostic criteria (RDC) for their definition has, in turn, led to inconsistent research findings for most phenotypes largely due to the variable definitions used for their ascertainment as discussed by the authors.
Abstract: Insomnia is a highly prevalent, often debilitating, and economically burdensome form of sleep disturbance caused by various situational, medical, emotional, environmental and behavioral factors. Although several consensually-derived nosologies have described numerous insomnia phenotypes, research concerning these phenotypes has been greatly hampered by a lack of widely accepted operational research diagnostic criteria (RDC) for their definition. The lack of RDC has, in turn, led to inconsistent research findings for most phenotypes largely due to the variable definitions used for their ascertainment. Given this problem, the American Academy of Sleep Medicine (AASM) commissioned a Work Group (WG) to review the literature and identify those insomnia phenotypes that appear most valid and tenable. In addition, this WG was asked to derive standardized RDC for these phenotypes and recommend assessment procedures for their ascertainment. This report outlines the WG's findings, the insomnia RDC derived, and research assessment procedures the WG recommends for identifying study participants who meet these RDC.
925 citations
TL;DR: In this article, a series of sulfonated poly(ether ether ketone)s (SPEEKs) were prepared by sulfonation of commercial Victrex ® and Gatone ® PEEK for a comparative study of proton exchange membranes (PEM) intended for fuel cell applications.
880 citations
TL;DR: It is shown that phosphorylation occurs rapidly over a large region around DNA double-strand breaks (DSBs) and leads to stepwise chromatin reconfiguration, allowing efficient DNA repair.
609 citations
TL;DR: In this paper, the authors found that dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes in children with acute lymphoblastic leukemia (ALL) but also injures myocardial cells.
Abstract: Background Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia (ALL) but also injures myocardial cells. Dexrazoxane, a free-radical scavenger, may protect the heart from doxorubicin-associated damage. Methods To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes, we randomly assigned 101 children with ALL to receive doxorubicin alone (30 mg per square meter of body-surface area every three weeks for 10 doses) and 105 to receive dexrazoxane (300 mg per square meter) followed immediately by doxorubicin. Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin. A total of 2377 serum samples (mean, 15.1 samples per patient) were obtained before, during, and after treatment with doxorubicin. Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated (>0.01 ng per milliliter) — the pr...
579 citations
University of Calgary1, University of Milan2, Semmelweis University3, University of Mainz4, Queen Mary University of London5, University of California, San Diego6, Goethe University Frankfurt7, Pennsylvania State University8, University of Toronto9, Laval University10, University of Alberta11, University of British Columbia12, St. John's University13, McMaster University14, Dalhousie University15, Ottawa Hospital16, Université de Montréal17, Halifax18, Queen's University19, University of Manitoba20, University of Auckland21, University of Cincinnati22, Odense University Hospital23, Duke University24, University of Tromsø25, Tel Aviv University26, University of Bern27, Peking Union Medical College Hospital28
TL;DR: Consensus approach is only an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches.
Abstract: C1 inhibitor deficiency (hereditary angioedema [HAE]) is a rare disorder for which there is a lack of consensus concerning diagnosis, therapy, and management, particularly in Canada. European initiatives have driven the approach to managing HAE with 3 C1-INH Deficiency Workshops held every 2 years in Hungary starting in 1999, with the third Workshop having recently been held in May 2003. The European Contact Board has established a European HAE Registry that will hopefully advance our knowledge of this disorder. The Canadian Hereditary Angioedema Society/Societe d'Angioedeme Hereditaire du Canada organized a Canadian International Consensus Conference held in Toronto, Ontario, Canada, on October 24 to 26, 2003, to foster consensus between major European and North American HAE treatment centers. Papers were presented by investigators from Europe and North America, and this consensus algorithm approach was discussed. There is a paucity of double-blind placebo-controlled trials in the treatment of HAE, making levels of evidence to support the algorithm less than optimal. Enclosed is the consensus algorithm approach recommended for the diagnosis, therapy, and management of HAE and agreed to by the authors of this article. This document is only a consensus algorithm approach and requires validation. As such, participants agreed to make this a living 2003 algorithm (ie, a work in progress) and agreed to review its content at future international HAE meetings. The consensus, however, has strength in that it was arrived at by the meeting of patient-care providers along with patient group representatives and individual patients reviewing information available to date and reaching agreement on how to approach the diagnosis, therapy, and management of HAE circa 2003. Hopefully evidence to support approaches to the management of HAE will approach the level of meta-analysis of randomized controlled trials in the near future.
575 citations
TL;DR: The NuA4 HAT complex is highly conserved in eukaryotes, in which it plays primary roles in transcription, cellular response to DNA damage, and cell cycle control.
Abstract: The NuA4 histone acetyltransferase (HAT) multisubunit complex is responsible for acetylation of histone H4 and H2A N-terminal tails in yeast. Its catalytic component, Esa1, is essential for cell cycle progression, gene-specific regulation and has been implicated in DNA repair. Almost all NuA4 subunits have clear homologues in higher eukaryotes, suggesting that the complex is conserved throughout evolution to metazoans. We demonstrate here that NuA4 complexes are indeed present in human cells. Tip60 and its splice variant Tip60b/PLIP were purified as stable HAT complexes associated with identical polypeptides, with 11 of the 12 proteins being homologs of yeast NuA4 subunits. This indicates a highly conserved subunit composition and the identified human proteins underline the role of NuA4 in the control of mammalian cell proliferation. ING3, a member of the ING family of growth regulators, links NuA4 to p53 function which we confirmed in vivo. Proteins specific to the human NuA4 complexes include ruvB-like helicases and a bromodomain-containing subunit linked to ligand-dependent transcription activation by the thyroid hormone receptor. We also demonstrate that subunits MRG15 and DMAP1 are present in distinct protein complexes harboring histone deacetylase and SWI2-related ATPase activities, respectively. Finally, analogous to yeast, a recombinant trimeric complex formed by Tip60, EPC1, and ING3 is sufficient to reconstitute robust nucleosomal HAT activity in vitro. In conclusion, the NuA4 HAT complex is highly conserved in eukaryotes, in which it plays primary roles in transcription, cellular response to DNA damage, and cell cycle control.
562 citations
TL;DR: DBPs predictive models are reviewed, their advantages and limitations are identified, and their potential applications as decision-making tools for water treatment analysis, epidemiological studies and regulatory concerns are examined.
TL;DR: An operational model of strategic alignment is proposed and empirically validated through a mail survey of 110 small firms and it was found that low-performance firms exhibited a conflictual coalignment pattern of business strategy, business structure, IT strategy, and IT structure that distinguished them from other firms.
TL;DR: Immobilization of probiotic cultures in whey protein-based microcapsules can increase cell survival when subjected to extreme conditions, making this approach potentially useful for delivery of viable bacteria to the gastrointestinal tract of humans via dairy fermented products.
TL;DR: It is suggested that increasing endogenous adiponectin levels has direct effects on insulin sensitivity and may induce similar physiological responses as prolonged treatment with peroxisomal proliferator-activated receptor gamma agonists.
Abstract: Adiponectin is a plasma protein expressed exclusively in adipose tissue. Adiponectin levels are linked to insulin sensitivity, but a direct effect of chronically elevated adiponectin on improved insulin sensitivity has not yet been demonstrated. We identified a dominant mutation in the collagenous domain of adiponectin that elevated circulating adiponectin values in mice by 3-fold. Adiponectinemia raised lipid clearance and lipoprotein lipase activity, and suppressed insulin-mediated endogenous glucose production. The induction of adiponectin during puberty and the sexual dimorphism in adult adiponectin values were preserved in these transgenic animals. As a result of elevated adiponectin, serum PRL values and brown adipose mass both increased. The effects on carbohydrate and lipid metabolism were associated with elevated phosphorylation of 5′-AMP-activated protein kinase in liver and elevated expression of peroxisomal proliferator-activated receptor γ2, caveolin-1, and mitochondrial markers in white adip...
TL;DR: Although TEE and PAEE were systematically underestimated during the 24 h period, the accelerometer assessed energy expenditure well during both the exercise period and the non-structured activities.
Abstract: Assessing the total energy expenditure (TEE) and the levels of physical activity in free-living conditions with non-invasive techniques remains a challenge. The purpose of the present study was to investigate the accuracy of a new uniaxial accelerometer for assessing TEE and physical-activity-related energy expenditure (PAEE) over a 24 h period in a respiratory chamber, and to establish activity levels based on the accelerometry ranges corresponding to the operationally defined metabolic equivalent (MET) categories. In study 1, measurement of the 24 h energy expenditure of seventy-nine Japanese subjects (40 (SD 12) years old) was performed in a large respiratory chamber. During the measurements, the subjects wore a uniaxial accelerometer (Lifecorder; Suzuken Co. Ltd, Nagoya, Japan) on their belt. Two moderate walking exercises of 30 min each were performed on a horizontal treadmill. In study 2, ten male subjects walked at six different speeds and ran at three different speeds on a treadmill for 4 min, with the same accelerometer. O2 consumption was measured during the last minute of each stage and was expressed in MET. The measured TEE was 8447 (SD 1337) kJ/d. The accelerometer significantly underestimated TEE and PAEE (91·9 (SD 5·4) and 92·7 (SD 17·8) % chamber value respectively); however, there was a significant correlation between the two values (r 0·928 and 0·564 respectively; P, 0·001). There was a strong correlation between the activity levels and the measured MET while walking (r 2 0·93; P, 0·001). Although TEE and PAEE were systematically underestimated during the 24 h period, the accelerometer assessed energy expenditure well during both the exercise period and the non-structured activities. Individual calibration factors may help to improve the accuracy of TEE estimation, but the average calibration factor for the group is probably sufficient for epidemiological research. This method is also important for assessing the diurnal profile of physical activity.
TL;DR: A real-time multiplex PCR assay which allows the detection of MRSA directly from clinical specimens containing a mixture of staphylococci in <1 h and was not inhibited in the presence of high copy numbers of MSSA, MRCoNS, or MSCoNS.
Abstract: Molecular methods for the rapid identification of methicillin-resistant Staphylococcus aureus (MRSA) are generally based on the detection of an S. aureus-specific gene target and the mecA gene. However, such methods cannot be applied for the direct detection of MRSA from nonsterile specimens such as nasal samples without the previous isolation, capture, or enrichment of MRSA because these samples often contain both coagulase-negative staphylococci (CoNS) and S. aureus, either of which can carry mecA. In this study, we describe a real-time multiplex PCR assay which allows the detection of MRSA directly from clinical specimens containing a mixture of staphylococci in <1 h. Five primers specific to the different staphylococcal cassette chromosome mec (SCCmec) right extremity sequences, including three new sequences, were used in combination with a primer and three molecular beacon probes specific to the S. aureus chromosomal orfX gene sequences located to the right of the SCCmec integration site. Of the 1,657 MRSA isolates tested, 1,636 (98.7%) were detected with the PCR assay, whereas 26 of 569 (4.6%) methicillin-susceptible S. aureus (MSSA) strains were misidentified as MRSA. None of the 62 nonstaphylococcal bacterial species or the 212 methicillin-resistant or 74 methicillin-susceptible CoNS strains (MRCoNS and MSCoNS, respectively) were detected by the assay. The amplification of MRSA was not inhibited in the presence of high copy numbers of MSSA, MRCoNS, or MSCoNS. The analytical sensitivity of the PCR assay, as evaluated with MRSA-negative nasal specimens containing a mixture of MSSA, MRCoNS, and MSCoNS spiked with MRSA, was ∼25 CFU per nasal sample. This real-time PCR assay represents a rapid and powerful method which can be used for the detection of MRSA directly from specimens containing a mixture of staphylococci.
TL;DR: In this paper, an optical sensor for detecting a target comprising a singlestranded aptamer complementary to the target, and a water-soluble cationic polythiophene derivative of the following formula: wherein n is an integer ranging from 6 to 100, is disclosed.
Abstract: An optical sensor for detecting a target comprising a singlestranded aptamer complementary to said target, and a water-soluble cationic polythiophene derivative of the following formula: wherein “n” is an integer ranging from 6 to 100, is disclosed The optical sensor allows for the detection of targets selected from the group consisting of potassium ions, small organic molecules, amino acids, proteins, whole cells and nucleotides The detection is based on the formation of hybrid anionic aptamer/cationic poly-thiophene complexes
TL;DR: In this paper, the authors characterize a class of polarization measures that fit into what they call the identityalienation framework, and simultanously satisfies a set of axioms, and provide sample estimators of population polarization indices that can be used to compare polarization across time or entities.
Abstract: distributions can be described using density functions. The main theorem uniquely characterizes a class of polarization measures that fits into what we call the “identityalienation” framework, and simultanously satisfies a set of axioms. Second, we provide sample estimators of population polarization indices that can be used to compare polarization across time or entities. Distribution-free statistical inference results are also used in order to ensure that the orderings of polarization across entities are not simply due to sampling noise. An illustration of the use of these tools using data from 21 countries shows that polarization and inequality orderings can often differ in practice.
TL;DR: The results indicate that the HIF-1 complex is involved in macrophage gene activation following LPS exposure and identify a novel pathway that could play a determinant role during inflammation and wound healing.
TL;DR: In this article, the extent of instrumental, conceptual, and symbolic use of university research in government agencies is investigated, and there are differences between the policy domains of the two domains.
Abstract: This article addresses three questions: What is the extent of instrumental, conceptual, and symbolic use of university research in government agencies? Are there differences between the policy doma...
TL;DR: In this article, the influence of the alloying elements and the different casting processes on the microstructure and performance of these alloys and corrosion was described, and a comprehensible approach for the resistance of these alloy alloys to general, localized and metallurgically influenced corrosion, which are the main challenges for their use was given.
Abstract: Magnesium (Mg) alloys as well as experimental alloys are emerging as light structural materials for current, new, and innovative applications. This paper describes the influence of the alloying elements and the different casting processes on the microstructure and performance of these alloys and corrosion. It gives a comprehensible approach for the resistance of these alloys to general, localized and metallurgically influenced corrosion, which are the main challenges for their use. Exposure to humid air with ∼65% relative humidity during 4 days gives 100–150 nm thickness. The film is amorphous and has an oxidation rate less than 0.01 µm/y. The pH values between 8.5 and 11.5 correspond to a relatively protective oxide or hydroxide film; however above 11.5 a passive stable layer is observed. The poor corrosion resistance of many Mg alloys can be due to the internal galvanic corrosion caused by second phases or impurities. Agitation or any other means of destroying or preventing the formation of a protective film leads to increasing corrosion kinetics. The pH changes during pitting corrosion can come from two different reduction reactions: reduction of dissolved oxygen (O) and that of hydrogen (H) ions. Filiform corrosion was observed in the uncoated AZ31, while general corrosion mainly occurred in some deposition coated alloys. Crevice corrosion can probably be initiated due to the hydrolysis reaction. Exfoliation can be considered as a type of intergranular attack, and this is observed in unalloyed Mg above a critical chloride concentration.
Journal Article•
TL;DR: New insight into antidepressant drug action suggests a novel approach to the development of antidepressant drugs.
Abstract: Major alterations of the hypothalamic–pituitary–adrenocortical (HPA) system that can be reversed by successful antidepressant therapy are often seen in depressed patients. Persuasive evidence points to the involvement of a dysfunctional glucocorticoid receptor (GR) system in these changes. Support for this also comes from studies of transgenic mice that express an antisense RNA, complementary to the GR mRNA, and have numerous neuroendocrine characteristics of human depression as well as altered behaviour. Many of these neuroendocrine and behavioural characteristics of the transgenic mice can be reversed by antidepressants. A possible explanation for this is that the antidepressant-induced increase in GRs renders the HPA axis more sensitive to glucocorticoid feedback. This new insight into antidepressant drug action suggests a novel approach to the development of antidepressant drugs.
TL;DR: The latest results regarding resistance mechanisms to drugs used in the clinic against Leishmania infections are discussed.
TL;DR: The NuA4 complex, first characterized in yeast, stands out as it controls multiple key nuclear functions in eukaryotic cells and contributes to the understanding of its diverse functions.
TL;DR: In this article, the authors provide a quantification of the main patterns of change of a subarctic peatland caused by permafrost decay monitored between 1957 and 2003.
Abstract: [1] In this study we provide a quantification of the main patterns of change of a subarctic peatland caused by permafrost decay monitored between 1957 and 2003. Up-thrusting of the peatland surface due to permafrost aggradation during the Little Ice Age resulted in the formation of an extensive peat plateau that gradually fragmented into residual palsas from the 19th century to the present. Only about 18% of the original surface occupied by permafrost was thawed in 1957, whereas only 13% was still surviving in 2003. Rapid permafrost melting over the last 50 years caused the concurrent formation of thermokarst ponds and fen-bog vegetation with rapid peat accumulation through natural successional processes of terrestrialization. The main climatic driver for accelerated permafrost thawing was snow precipitation which increased from 1957 to present while annual and seasonal temperatures remained relatively stable until about the mid-1990s when annual temperature rose well above the mean. Contrary to current expectations, the melting of permafrost caused by recent climate change does not transform the peatland to a carbon-source ecosystem as rapid terrestrialization exacerbates carbon-sink conditions and tends to balance the local carbon budget.
TL;DR: The aim of this study was to evaluate the efficacy and safety of omalizumab in patients with concomitant moderate‐to‐severe asthma and persistent allergic rhinitis.
Abstract: Background: Anti-IgE therapy could be particularly beneficial for patients with concomitant disease as it targets a common factor in both diseases. The aim of this study was to evaluate the efficacy and safety of omalizumab in patients with concomitant moderate-to-severe asthma and persistent allergic rhinitis. Methods: This multicentre, randomized, double-blind, parallel-group, placebocontrolled trial evaluated the safety and efficacy of omalizumab. A total of 405 patients (12–74 years) with a stable treatment (‡ 400 lg budesonide Turbuhaler � )a nd‡ 2 unscheduled medical visits for asthma during the past year or ‡ 3 during the past 2 years were enrolled. Patients received omalizumab (‡ 0.016 mg/kg/IgE [IU/ml] per 4 weeks) or placebo for 28 weeks. Results: Fewer patients treated with omalizumab experienced asthma exacerbations (20.6%) than placebo-treated patients (30.1%), P ¼ 0.02. A clinically significant (‡ 1.0 point) improvement in both Asthma Quality of Life Questionnaire and Rhinitis Quality of Life Questionnaire occurred in 57.7% of omalizumab patients compared with 40.6% of placebo patients (P < 0.001). Omalizumab reduced Wasserfallen symptom scores for asthma (P ¼ 0.023), rhinitis (P < 0.001) and the composite asthma/rhinitis scores (P < 0.001) compared with placebo. Serious adverse events were observed in 1.4% of omalizumab-treated patients and 1.5% of placebo-treated patients. Conclusion: Omalizumab is well tolerated and effective in preventing asthma exacerbations and improving quality of life in patients with concomitant asthma and persistent allergic rhinitis.
08 Jun 2004
TL;DR: A metric is studied between labelled Markov processes that has the property that processes are at zero distance if and only if they are bisimilar and is related, in spirit, to the Hutchinson metric.
Abstract: The notion of process equivalence of probabilistic processes is sensitive to the exact probabilities of transitions. Thus, a slight change in the transition probabilities will result in two equivalent processes being deemed no longer equivalent. This instability is due to the quantitative nature of probabilistic processes. In a situation where the process behavior has a quantitative aspect there should be a more robust approach to process equivalence. This paper studies a metric between labelled Markov processes. This metric has the property that processes are at zero distance if and only if they are bisimilar. The metric is inspired by earlier work on logics for characterizing bisimulation and is related, in spirit, to the Hutchinson metric.
TL;DR: Examination of inter‐species comparisons indicates that the proportion of muscle fibres occupied by mitochondria increases at low temperatures, most clearly in moderately active demersal species, and compensatory increases in the protein‐specific rates of mitochondrial substrate oxidation maintain constant capacities except at winter extremes.
Abstract: For most fish, body temperature is very close to that of the habitat. The diversity of thermal habitats exploited by fish as well as their capacity to adapt to thermal change makes them excellent organisms in which to examine the evolutionary and phenotypic responses to temperature. An extensive literature links cold temperatures with enhanced oxidative capacities in fish tissues, particularly skeletal muscle. Closer examination of inter-species comparisons (i.e. the evolutionary perspective) indicates that the proportion of muscle fibres occupied by mitochondria increases at low temperatures, most clearly in moderately active demersal species. Isolated muscle mitochondria show no compensation of protein-specific rates of substrate oxidation during evolutionary adaptation to cold temperatures. During phenotypic cold acclimation, mitochondrial volume density increases in oxidative muscle of some species (striped bass Morone saxatilis, crucian carp Carassius carassius), but remains stable in others (rainbow trout Oncorhynchus mykiss). A role for the mitochondrial reticulum in distributing oxygen through the complex architecture of skeletal muscle fibres may explain mitochondrial proliferation. In rainbow trout, compensatory increases in the protein-specific rates of mitochondrial substrate oxidation maintain constant capacities except at winter extremes. Changes in mitochondrial properties (membrane phospholipids, enzymatic complement and cristae densities) can enhance the oxidative capacity of muscle in the absence of changes in mitochondrial volume density. Changes in the unsaturation of membrane phospholipids are a direct response to temperature and occur in isolated cells. This fundamental response maintains the dynamic phase behaviour of the membrane and adjusts the rates of membrane processes. However, these adjustments may have deleterious consequences. For fish living at low temperatures, the increased polyunsaturation of mitochondrial membranes should raise rates of mitochondrial respiration which would in turn enhance the formation of reactive oxygen species (ROS), increase proton leak and favour peroxidation of these membranes. Minimisation of mitochondrial oxidative capacities in organisms living at low temperatures would reduce such damage.
TL;DR: This is the tenth update of the human obesity gene map, incorporating published results up to the end of October 2003 and continuing the previous format.
Abstract: This is the tenth update of the human obesity gene map, incorporating published results up to the end of October 2003 and continuing the previous format. Evidence from single-gene mutation obesity cases, Mendelian disorders exhibiting obesity as a clinical feature, quantitative trait loci (QTLs) from human genome-wide scans and animal crossbreeding experiments, and association and linkage studies with candidate genes and other markers is reviewed. Transgenic and knockout murine models relevant to obesity are also incorporated (N = 55). As of October 2003, 41 Mendelian syndromes relevant to human obesity have been mapped to a genomic region, and causal genes or strong candidates have been identified for most of these syndromes. QTLs reported from animal models currently number 183. There are 208 human QTLs for obesity phenotypes from genome-wide scans and candidate regions in targeted studies. A total of 35 genomic regions harbor QTLs replicated among two to five studies. Attempts to relate DNA sequence variation in specific genes to obesity phenotypes continue to grow, with 272 studies reporting positive associations with 90 candidate genes. Fifteen such candidate genes are supported by at least five positive studies. The obesity gene map shows putative loci on all chromosomes except Y. Overall, more than 430 genes, markers, and chromosomal regions have been associated or linked with human obesity phenotypes. The electronic version of the map with links to useful sites can be found at http:obesitygene.pbrc.edu.
TL;DR: The systemically transplanted stem cells that express green fluorescent protein into lethally irradiated mice and found that these cells immigrated into the brain parenchyma of many regions of the CNS, suggesting that microglia of blood origin could activate cells of the adaptive immune system and cause harm to the CNS.
Abstract: Pluripotent stem cells can differentiate into a variety of cell types during tissue development and regeneration. However, it is still unclear whether bone marrow-derived stem cells can migrate across the blood-brain barrier in many regions of the central nervous system (CNS) and if these cells can readily differentiate into functional parenchymal microglia. We thus studied the differentiation fate of bone marrow stem cells upon immigration into the CNS. To this end, we systemically transplanted stem cells that express green fluorescent protein (GFP) into lethally irradiated mice and found that these cells immigrated into the brain parenchyma of many regions of the CNS. Nearly all of the infiltrating cells had a highly ramified morphology and colocalized with the microglial marker iba1. Moreover, these cells expressed high levels of the protein CD11c, indicating that microglia of bone marrow origin may be potent antigen presenting cells. These data suggest that microglia of blood origin could activate cells of the adaptive immune system and cause harm to the CNS. Therefore, these results may have great clinical relevance for both immune-derived neuronal disorders and cancer patients undergoing allogeneic hematopoietic stem-cell transplantation.