Showing papers by "RMIT University published in 2008"
TL;DR: The authors proposes ways to use program theory for evaluating aspects of programs that are complicated or complex. But they do not discuss the differences between what is complicated (multiple components) and what is complex (emergent).
Abstract: This article proposes ways to use programme theory for evaluating aspects of programmes that are complicated or complex. It argues that there are useful distinctions to be drawn between aspects that are complicated and those that are complex, and provides examples of programme theory evaluations that have usefully represented and address both of these. While complexity has been defined in varied ways in previous discussions of evaluation theory and practice, this article draws on Glouberman and Zimmerman's conceptualization of the differences between what is complicated (multiple components) and what is complex (emergent). Complicated programme theory may be used to represent interventions with multiple components, multiple agencies, multiple simultaneous causal strands and/or multiple alternative causal strands. Complex programme theory may be used to represent recursive causality (with reinforcing loops), disproportionate relationships (where at critical levels, a small change can make a big difference ...
755 citations
TL;DR: In this paper, the authors describe and explain, using a combination of interviews and content analysis, the social and environmental reporting practices of a major garment export organisation within a developing country, and find that particular stakeholder groups have, since the early 1990s, placed pressure on the Bangladeshi clothing industry in terms of its social performance.
Abstract: Purpose – The aim of the paper is to describe and explain, using a combination of interviews and content analysis, the social and environmental reporting practices of a major garment export organisation within a developing country.Design/methodology/approach – Senior executives from a major organisation in Bangladesh are interviewed to determine the pressures being exerted on them in terms of their social and environmental performance. The perceptions of pressures are then used to explain – via content analysis – changing social and environmental disclosure practices.Findings – The results show that particular stakeholder groups have, since the early 1990s, placed pressure on the Bangladeshi clothing industry in terms of its social performance. This pressure, which is also directly related to the expectations of the global community, in turn drives the industry's social policies and related disclosure practices.Research limitations/implications – The findings show that, within the context of a developing ...
594 citations
TL;DR: Sedentary lifestyle patterns in children and adolescents, i.e. playing digital games, using computers and especially watching television, have been associated with obesity, but not all sedentary behaviour has shown the same relevance to, and relationship with, obesity.
Abstract: Sedentary lifestyle patterns in children and adolescents, i.e. playing digital games, using computers and especially watching television, have been associated with obesity. However, not all sedentary behaviour has shown the same relevance to, and relationship with, obesity. Therefore, we conducted a review including published studies found in PubMed and other medical journals, dated between January 1990 and April 2007. The ages of the children and adolescents who were the object of the study ranged between 2 and 18 years. For the purpose of this paper, we selected cross-sectional, longitudinal and intervention studies. Sufficient evidence exists to recommend setting a limit to the time spent watching TV, especially for younger children. However, video games and computers do not represent such a high risk compared to watching TV, when they do not replace physical activity too much. In fact, there is no evidence to suggest that sedentary behaviour displaces physical activity levels. Mechanisms that explain the link between sedentariness and obesity are also discussed. Finally, future studies should take into account important mediators such as socioeconomic status and family structure.
593 citations
TL;DR: A new effectiveness metric, rank-biased precision, is introduced that is derived from a simple model of user behavior, is robust if answer rankings are extended to greater depths, and allows accurate quantification of experimental uncertainty, even when only partial relevance judgments are available.
Abstract: A range of methods for measuring the effectiveness of information retrieval systems has been proposed. These are typically intended to provide a quantitative single-value summary of a document ranking relative to a query. However, many of these measures have failings. For example, recall is not well founded as a measure of satisfaction, since the user of an actual system cannot judge recall. Average precision is derived from recall, and suffers from the same problem. In addition, average precision lacks key stability properties that are needed for robust experiments. In this article, we introduce a new effectiveness metric, rank-biased precision, that avoids these problems. Rank-biased pre-cision is derived from a simple model of user behavior, is robust if answer rankings are extended to greater depths, and allows accurate quantification of experimental uncertainty, even when only partial relevance judgments are available.
584 citations
TL;DR: The study of interactions of newly synthesized compounds with CYP3A4 has been incorporated into drug development and detection of possible CYP 3A4 inhibitors and inducers during the early stages of drug development is critical in preventing potential drug-drug interactions and side effects.
Abstract: Human cytochrome P450 (CYP) 3A4 is the most abundant hepatic and intestinal phase I enzyme that metabolizes approximately 50% marketed drugs. The crystal structure of bound and unbound CYP3A4 has been recently constructed, and a small active site and a peripheral binding site are identified. A recent study indicates that CYP3A4 undergoes dramatic conformational changes upon binding to ketoconazole or erythromycin with a differential but substantial (>80%) increase in the active site volume, providing a structural basis for ligand promiscuity of CYP3A4. A number of important drugs have been identified as substrates, inducers and/or inhibitors of CYP3A4. The ability of drugs to act as inducers, inhibitors, or substrates for CYP3A is predictive of whether concurrent administration of these compounds with a known CYP3A substrate might lead to altered drug disposition, efficacy or toxicity. The substrates of CYP3A4 considerably overlap with those of P-glycoprotein (P-gp). To date, the identified clinically important CYP3A4 inhibitors mainly include macrolide antibiotics (e.g., clarithromycin, and erythromycin), anti-HIV agents (e.g., ritonavir and delavirdine), antidepressants (e.g. fluoxetine and fluvoxamine), calcium channel blockers (e.g. verapamil and diltiazem), steroids and their modulators (e.g., gestodene and mifepristone), and several herbal and dietary components. Many of these drugs are also mechanism-based inhibitors of CYP3A4, which involves formation of reactive metabolites, binding to CYP3A4 and irreversible enzyme inactivation. A small number of drugs such as rifampin, phenytoin and ritonavir are identified as inducers of CYP3A4. The orphan nuclear receptor, pregnane X receptor (PXR), have been found to play a critical role in the induction of CYP3A4. The inhibition or induction of CYP3A4 by drugs often causes unfavorable and long-lasting drug-drug interactions and probably fatal toxicity, depending on many factors associated with the enzyme, drugs and the patients. The study of interactions of newly synthesized compounds with CYP3A4 has been incorporated into drug development and detection of possible CYP3A4 inhibitors and inducers during the early stages of drug development is critical in preventing potential drug-drug interactions and side effects. Clinicians are encouraged to have a sound knowledge on drugs that behave as substrates, inhibitors or inducers of CYP3A4, and take proper cautions and close monitoring for potential drug interactions when using drugs that are CYP3A4 inhibitors or inducers.
524 citations
TL;DR: Altered P-gp/MDR1 activity due to induction and/or inhibition can cause drug–drug interactions with altered drug pharmacokinetics and response, and is of great clinical importance in non-cancer-related drug therapy due to its wide-ranging effects on the absorption and excretion of a variety of drugs.
Abstract: 1. P-glycoprotein (P-gp/MDR1), one of the most clinically important transmembrane transporters in humans, is encoded by the ABCB1/MDR1 gene. Recent insights into the structural features of P-gp/MDR...
497 citations
TL;DR: Interleukin‐10 is a cytokine with broad anti‐inflammatory properties by its suppression of both macrophage and dendritic cell function, including antigen‐presenting cell function and the production of proinflammatory cytokines, which shows great potential as adjuvants in preventative or therapeutic vaccines against chronic infection or cancer.
Abstract: Summary: Interleukin-10 (IL-10) is a cytokine with broad anti-inflammatory properties by its suppression of both macrophage and dendritic cell function, including antigen-presenting cell function and the production of proinflammatory cytokines. This can result subsequently in the feedback regulation of both T-helper 1 (Th1)-type and Th2-type responses. This review discusses the potential use of IL-10 or agents that induce IL-10 as potential anti-inflammatory therapies in inflammatory diseases. Although IL-10-deficient mice develop colitis in the presence of normal gut flora and clear certain intracellular pathogens more efficiently, this is often accompanied by immunopathology, which can be lethal to the host. This reinforces the anti-inflammatory properties of IL-10, although it should be noted that as discussed below, IL-10 can also promote B-cell and other immune responses under particular settings. A penalty of its role to limit the immune and inflammatory responses to pathogens and prevent damage to the host is that high or dysregulated levels of IL-10 may result in chronic infection. Thus, antagonists of IL-10 show great potential as adjuvants in preventative or therapeutic vaccines against chronic infection or cancer. This article reviews basic published studies on IL-10, which may lead to potential uses of IL-10 or its antagonists in human disease.
423 citations
TL;DR: The authors investigated the relationship between primary school teachers' self-reported and actual use of classroom management strategies, and examined how the use of proactive and reactive strategies is related to teacher stress and student behaviour.
Abstract: This study investigated the relationship between primary school teachers’ self‐reported and actual use of classroom management strategies, and examined how the use of proactive and reactive strategies is related to teacher stress and student behaviour. The total sample consisted of 97 teachers from primary schools within Melbourne. Teachers completed four questionnaires which gathered information on demographics, disruptive student behaviour, teacher management strategies, and teacher self‐reported stress. In addition, 20 of the 97 teachers were observed in their classrooms while teaching, with teacher behaviour management strategies and student on‐task behaviour recorded. Observation and questionnaire data were then matched. The findings indicated that teacher self‐reports accurately reflect actual practice, that relatively minor forms of student misbehaviours are a common concern for teachers, and that teachers are spending a considerable amount of time on behaviour management issues. The findings also ...
420 citations
TL;DR: P Pulse radiolysis studies of early stages of melanogenesis indicate that mixed melanogenesis proceeds in three distinct stages—the initial production of cysteinyldopas, followed by their oxidation to produce pheomelanin, followed finally by the production of eumelan in.
Abstract: Melanins can be classified into two major groups—insoluble brown to black pigments termed eumelanin and alkali-soluble yellow to reddish-brown pigments termed pheomelanin. Both types of pigment derive from the common precursor dopaquinone (ortho-quinone of 3,4-dihydroxyphenylalanine) which is formed via the oxidation of L-tyrosine by the melanogenic enzyme tyrosinase. Dopaquinone is a highly reactive ortho-quinone that plays pivotal roles in the chemical control of melanogenesis. In the absence of sulfhydryl compounds, dopaquinone undergoes intramolecular cyclization to form cyclodopa, which is then rapidly oxidized by a redox reaction with dopaquinone to give dopachrome (and dopa). Dopachrome then gradually and spontaneously rearranges to form 5,6-dihydroxyindole and to a lesser extent 5,6-dihydroxyindole-2-carboxylic acid, the ratio of which is determined by a distinct melanogenic enzyme termed dopachrome tautomerase (tyrosinase-related protein-2). Oxidation and subsequent polymerization of these dihydroxyindoles leads to the production of eumelanin. However, when cysteine is present, this process gives rise preferentially to the production of cysteinyldopa isomers. Cysteinyldopas are subsequently oxidized through redox reaction with dopaquinone to form cysteinyldopaquinones that eventually lead to the production of pheomelanin. Pulse radiolysis studies of early stages of melanogenesis (involving dopaquinone and cysteine) indicate that mixed melanogenesis proceeds in three distinct stages—the initial production of cysteinyldopas, followed by their oxidation to produce pheomelanin, followed finally by the production of eumelanin. Based on these data, a casing model of mixed melanogenesis is proposed in which a preformed pheomelanic core is covered by a eumelanic surface.
416 citations
TL;DR: This chapter focuses on two of the most successful examples of optimization techniques inspired by swarm intelligence: ant colony optimization and particle swarm optimization.
Abstract: Optimization techniques inspired by swarm intelligence have become increasingly popular during the last decade. They are characterized by a decentralized way of working that mimics the behavior of swarms of social insects, flocks of birds, or schools of fish. The advantage of these approaches over traditional techniques is their robustness and flexibility. These properties make swarm intelligence a successful design paradigm for algorithms that deal with increasingly complex problems. In this chapter we focus on two of the most successful examples of optimization techniques inspired by swarm intelligence: ant colony optimization and particle swarm optimization. Ant colony optimization was introduced as a technique for combinatorial optimization in the early 1990s. The inspiring source of ant colony optimization is the foraging behavior of real ant colonies. In addition, particle swarm optimization was introduced for continuous optimization in the mid-1990s, inspired by bird flocking.
389 citations
TL;DR: The authors examined how consumers assess the claims of Trappist and Abbey beer brands and identified three forms of authenticity: pure (literal) authenticity, approximate authenticity, and moral authenticity.
Abstract: Authenticity is a cornerstone of contemporary marketing. Yet how do firms develop brand positions based on authenticity when marketing, and in particular, advertising, is believed to be antithetical to such positioning? We examine how consumers assess the claims of Trappist and Abbey beer brands. We identify three forms of authenticity: pure (literal) authenticity, approximate authenticity, and moral authenticity. In each case, consumers draw on either indexical or iconic cues to form judgments of authenticity, although the type of cue and degree of abstraction differ across the three types. We also find that the informants are duped by careful advertisements, and explain this by proposing that the relationships between indexical and iconic cues are closer than previously thought.
RMIT University1, Rutgers University2, Lehman College3, University of Central Florida4, University of South Florida5, University of Mary Hardin–Baylor6, Florida International University7, University of North Carolina at Chapel Hill8, Texas A&M University9, Baylor University10, Skidmore College11, Kennesaw State University12, Florida State University13, University of KwaZulu-Natal14, California State University, Northridge15, Nova Southeastern University16
TL;DR: The timing of the energy intake and the ratio of certain ingested macronutrients are likely the attributes which allow for enhanced recovery and tissue repair following high-volume exercise, augmented muscle protein synthesis, and improved mood states when compared with unplanned or traditional strategies of nutrient intake.
Abstract: Position Statement: The position of the Society regarding nutrient timing and the intake of carbohydrates, proteins, and fats in reference to healthy, exercising individuals is summarized by the following eight points: 1.) Maximal endogenous glycogen stores are best promoted by following a high-glycemic, high-carbohydrate (CHO) diet (600 – 1000 grams CHO or ~8 – 10 g CHO/kg/d), and ingestion of free amino acids and protein (PRO) alone or in combination with CHO before resistance exercise can maximally stimulate protein synthesis. 2.) During exercise, CHO should be consumed at a rate of 30 – 60 grams of CHO/hour in a 6 – 8% CHO solution (8 – 16 fluid ounces) every 10 – 15 minutes. Adding PRO to create a CHO:PRO ratio of 3 – 4:1 may increase endurance performance and maximally promotes glycogen re-synthesis during acute and subsequent bouts of endurance exercise. 3.) Ingesting CHO alone or in combination with PRO during resistance exercise increases muscle glycogen, offsets muscle damage, and facilitates greater training adaptations after either acute or prolonged periods of supplementation with resistance training. 4.) Post-exercise (within 30 minutes) consumption of CHO at high dosages (8 – 10 g CHO/kg/day) have been shown to stimulate muscle glycogen re-synthesis, while adding PRO (0.2 g – 0.5 g PRO/kg/day) to CHO at a ratio of 3 – 4:1 (CHO: PRO) may further enhance glycogen re-synthesis. 5.) Post-exercise ingestion (immediately to 3 h post) of amino acids, primarily essential amino acids, has been shown to stimulate robust increases in muscle protein synthesis, while the addition of CHO may stimulate even greater levels of protein synthesis. Additionally, pre-exercise consumption of a CHO + PRO supplement may result in peak levels of protein synthesis. 6.) During consistent, prolonged resistance training, post-exercise consumption of varying doses of CHO + PRO supplements in varying dosages have been shown to stimulate improvements in strength and body composition when compared to control or placebo conditions. 7.) The addition of creatine (Cr) (0.1 g Cr/kg/day) to a CHO + PRO supplement may facilitate even greater adaptations to resistance training. 8.) Nutrient timing incorporates the use of methodical planning and eating of whole foods, nutrients extracted from food, and other sources. The timing of the energy intake and the ratio of certain ingested macronutrients are likely the attributes which allow for enhanced recovery and tissue repair following high-volume exercise, augmented muscle protein synthesis, and improved mood states when compared with unplanned or traditional strategies of nutrient intake.
TL;DR: EPA was effective in reducing the incidence of CAD events for patients with this dyslipidemic pattern, suggesting that EPA may be especially beneficial in patients who with abnormal TG and HDL-C levels.
TL;DR: The results suggest that IL-17A is a newly discovered effector molecule produced by TCR γδ T cells, which is important in innate immunity in the liver, similar to the distinction between Th17 and Th1 in CD4+ T cells.
Abstract: IL-17A is originally identified as a proinflammatory cytokine that induces neutrophils. Although IL-17A production by CD4+ Th17 T cells is well documented, it is not clear whether IL-17A is produced and participates in the innate immune response against infections. In the present report, we demonstrate that IL-17A is expressed in the liver of mice infected with Listeria monocytogenes from an early stage of infection. IL-17A is important in protective immunity at an early stage of listerial infection in the liver because IL-17A-deficient mice showed aggravation of the protective response. The major IL-17A-producing cells at the early stage were TCR γδ T cells expressing TCR Vγ4 or Vγ6. Interestingly, TCR γδ T cells expressing both IFN-γ and IL-17A were hardly detected, indicating that the IL-17A-producing TCR γδ T cells are distinct from IFN-γ-producing γδ T cells, similar to the distinction between Th17 and Th1 in CD4+ T cells. All the results suggest that IL-17A is a newly discovered effector molecule produced by TCR γδ T cells, which is important in innate immunity in the liver.
TL;DR: The overall DFS was significantly better after an AS, especially when the size of HCC ranges from 2 to 5 cm, and further stratification according to liver damage did not show any significant differences between an AS and an MH.
TL;DR: It can be expected that modulation of MRP members may represent a useful approach in the management of anticancer and antimicrobial drug resistance and possibly of inflammatory diseases and other diseases.
Abstract: Human contains 49 ATP-binding cassette (ABC) transporter genes and the multidrug resistance associated proteins (MRP1/ABCC1, MRP2/ABCC2, MRP3/ABCC3, MRP4/ABCC4, MRP5/ABCC5, MRP6/ABCC6, MRP7/ABCC10, MRP8/ABCC11 and MRP9/ABCC12) belong to the ABCC family which contains 13 members. ABCC7 is cystic fibrosis transmembrane conductance regulator; ABCC8 and ABCC9 are the sulfonylurea receptors which constitute the ATP-sensing subunits of a complex potassium channel. MRP10/ABCC13 is clearly a pseudo-gene which encodes a truncated protein that is highly expressed in fetal human liver with the highest similarity to MRP2/ABCC2 but without transporting activity. These transporters are localized to the apical and/or basolateral membrane of the hepatocytes, enterocytes, renal proximal tubule cells and endothelial cells of the blood-brain barrier. MRP/ABCC members transport a structurally diverse array of important endogenous substances and xenobiotics and their metabolites (in particular conjugates) with different substrate specificity and transport kinetics. The human MRP/ABCC transporters except MRP9/ABCC12 are all able to transport organic anions, such as drugs conjugated to glutathione, sulphate or glucuronate. In addition, selected MRP/ABCC members may transport a variety of endogenous compounds, such as leukotriene C(4) (LTC(4) by MRP1/ABCC1), bilirubin glucuronides (MRP2/ABCC2, and MRP3/ABCC3), prostaglandins E1 and E2 (MRP4/ABCC4), cGMP (MRP4/ABCC4, MRP5/ABCC5, and MRP8/ABCC11), and several glucuronosyl-, or sulfatidyl steroids. In vitro, the MRP/ABCC transporters can collectively confer resistance to natural product anticancer drugs and their conjugated metabolites, platinum compounds, folate antimetabolites, nucleoside and nucleotide analogs, arsenical and antimonial oxyanions, peptide-based agents, and in concert with alterations in phase II conjugating or biosynthetic enzymes, classical alkylating agents, alkylating agents. Several MRP/ABCC members (MRPs 1-3) are associated with tumor resistance which is often caused by an increased efflux and decreased intracellular accumulation of natural product anticancer drugs and other anticancer agents. Drug targeting of these transporters to overcome MRP/ABCC-mediated multidrug resistance may play a role in cancer chemotherapy. Most MRP/ABCC transporters are subject to inhibition by a variety of compounds. Based on currently available preclinical and limited clinical data, it can be expected that modulation of MRP members may represent a useful approach in the management of anticancer and antimicrobial drug resistance and possibly of inflammatory diseases and other diseases. A better understanding of their substrates and inhibitors has important implications in development of drugs for treatment of cancer and inflammation.
TL;DR: The Cooperative Research Centre for Advanced Composite Structures (CRC-ACS) is leading a currently running collaborative project to develop a methodology for determining mechanical behaviour and failure in composite structures as discussed by the authors.
TL;DR: It is demonstrated that lipid identification based on CID alone belies the natural structural diversity in lipid biochemistry and the potential of OzID as a complementary approach within automated, high-throughput lipid analysis protocols is illustrated.
Abstract: Ions formed from lipids during electrospray ionization of crude lipid extracts have been mass-selected within a quadrupole linear ion trap mass spectrometer and allowed to react with ozone vapor. Gas-phase ion−molecule reactions between unsaturated lipid ions and ozone are found to yield two primary product ions for each carbon−carbon double bond within the molecule. The mass-to-charge ratios of these chemically induced fragments are diagnostic of the position of unsaturation within the precursor ion. This novel analytical technique, dubbed ozone-induced dissociation (OzID), can be applied both in series and in parallel with conventional collision-induced dissociation (CID) to provide near-complete structural assignment of unknown lipids within complex mixtures without prior fractionation or derivatization. In this study, OzID is applied to a suite of complex lipid extracts from sources including human lens, bovine kidney, and commercial olive oil, thus demonstrating the technique to be applicable to a br...
TL;DR: Accumulating data are documenting an inverse relationship between immune status, response to vaccination, health, and longevity, suggesting that the immune system becomes less effective with advancing age and that this is clinically relevant.
Abstract: Accumulating data are documenting an inverse relationship between immune status, response to vaccination, health, and longevity, suggesting that the immune system becomes less effective with advancing age and that this is clinically relevant. The mechanisms and consequences of age-associated immune alterations, designated immunosenescence, are briefly reviewed here.
TL;DR: The study has revealed that E. coli in raw foods is a significant reservoir of resistance and virulence genes.
TL;DR: Continuous glucose monitoring during pregnancy is associated with improved glycaemic control in the third trimester, lower birth weight, and reduced risk of macrosomia.
Abstract: Objective To evaluate the effectiveness of continuous glucose monitoring during pregnancy on maternal glycaemic control, infant birth weight, and risk of macrosomia in women with type 1 and type 2 diabetes. Design Prospective, open label randomised controlled trial. Setting Two secondary care multidisciplinary obstetric clinics for diabetes in the United Kingdom. Participants 71 women with type 1 diabetes (n=46) or type 2 diabetes (n=25) allocated to antenatal care plus continuous glucose monitoring (n=38) or to standard antenatal care (n=33). Intervention Continuous glucose monitoring was used as an educational tool to inform shared decision making and future therapeutic changes at intervals of 4-6 weeks during pregnancy. All other aspects of antenatal care were equal between the groups. Main outcome measures The primary outcome was maternal glycaemic control during the second and third trimesters from measurements of HbA 1c levels every four weeks. Secondary outcomes were birth weight and risk of macrosomia using birthweight standard deviation scores and customised birthweight centiles. Statistical analyses were done on an intention to treat basis. Results Women randomised to continuous glucose monitoring had lower mean HbA 1c levels from 32 to 36 weeks’ gestation compared with women randomised to standard antenatal care: 5.8% (SD 0.6) v 6.4% (SD 0.7). Compared with infants of mothers in the control arm those of mothers in the intervention arm had decreased mean birthweight standard deviation scores (0.9 v 1.6; effect size 0.7 SD, 95% confidence interval 0.0 to 1.3), decreased median customised birthweight centiles (69% v 93%), and a reduced risk of macrosomia (odds ratio 0.36, 95% confidence interval 0.13 to 0.98). Conclusion Continuous glucose monitoring during pregnancy is associated with improved glycaemic control in the third trimester, lower birth weight, and reduced risk of macrosomia. Trial registration Current Controlled Trials ISRCTN84461581.
TL;DR: It is demonstrated that retrotransposon-derived Rtl1 (retrotranspos on-like 1), also known as Peg11 (paternally expressed 11), is essential for maintenance of the fetal capillaries, and that both its loss and its overproduction cause late-fetal and/or neonatal lethality in mice.
Abstract: Eutherian placenta, an organ that emerged in the course of mammalian evolution, provides essential architecture, the so-called feto-maternal interface, for fetal development by exchanging nutrition, gas and waste between fetal and maternal blood. Functional defects of the placenta cause several developmental disorders, such as intrauterine growth retardation in humans and mice. A series of new inventions and/or adaptations must have been necessary to form and maintain eutherian chorioallantoic placenta, which consists of capillary endothelial cells and a surrounding trophoblast cell layer(s). Although many placental genes have been identified, it remains unknown how the feto-maternal interface is formed and maintained during development, and how this novel design evolved. Here we demonstrate that retrotransposon-derived Rtl1 (retrotransposon-like 1), also known as Peg11 (paternally expressed 11), is essential for maintenance of the fetal capillaries, and that both its loss and its overproduction cause late-fetal and/or neonatal lethality in mice.
TL;DR: While selected markers of training adaptation were enhanced with twice a day training, the performance of a 1-h time trial undertaken after a 60-min steady-state ride was similar after once daily or twice every second day training programs.
Abstract: We determined the effects of a cycle training program in which selected sessions were performed with low muscle glycogen content on training capacity and subsequent endurance performance, whole body substrate oxidation during submaximal exercise, and several mitochondrial enzymes and signaling proteins with putative roles in promoting training adaptation. Seven endurance-trained cyclists/triathletes trained daily (High) alternating between 100-min steady-state aerobic rides (AT) one day, followed by a high-intensity interval training session (HIT; 8 × 5 min at maximum self-selected effort) the next day. Another seven subjects trained twice every second day (Low), first undertaking AT, then 1–2 h later, the HIT. These training schedules were maintained for 3 wk. Forty-eight hours before and after the first and last training sessions, all subjects completed a 60-min steady-state ride (60SS) followed by a 60-min performance trial. Muscle biopsies were taken before and after 60SS, and rates of substrate oxidation were determined throughout this ride. Resting muscle glycogen concentration (412 ± 51 vs. 577 ± 34 μmol/g dry wt), rates of whole body fat oxidation during 60SS (1,261 ± 247 vs. 1,698 ± 174 μmol·kg−1·60 min−1), the maximal activities of citrate synthase (45 ± 2 vs. 54 ± 1 mmol·kg dry wt−1·min−1), and β-hydroxyacyl-CoA-dehydrogenase (18 ± 2 vs. 23 ± 2 mmol·kg dry wt−1·min−1) along with the total protein content of cytochrome c oxidase subunit IV were increased only in Low (all P < 0.05). Mitochondrial DNA content and peroxisome proliferator-activated receptor-γ coactivator-1α protein levels were unchanged in both groups after training. Cycling performance improved by ∼10% in both Low and High. We conclude that compared with training daily, training twice every second day compromised high-intensity training capacity. While selected markers of training adaptation were enhanced with twice a day training, the performance of a 1-h time trial undertaken after a 60-min steady-state ride was similar after once daily or twice every second day training programs.
TL;DR: In this paper, three proposed models were tested by Confirmatory Factor Analysis (CFA) using the multi-data source of 138 cases, and the overall fit of the nine-correlated factor model, on its second test, was statistically significant and that indicated that the Full Leadership Model (nine correlated leadership model) could be the most appropriately and adequately capturing the factor constructs of transformationaltransactional leadership.
Abstract: Most previous research on transformational leadership involved the use of the “Multifactor Leadership Questionnaire” (MLQ) to measure various aspects of transformational-transactional leadership. Although the MLQ is widely used, the instrument has been criticized in some areas of its measurement factors. In this study, three proposed models were tested by Confirmatory Factor Analysis (CFA) using the multi-data source of 138 cases. Results revealed that the overall fit of the nine-correlated factor model, on its second test, was statistically significant and that indicated that the Full Leadership Model (nine-correlated leadership model) could be the most appropriately and adequately capturing the factor constructs of transformational-transactional leadership.
Keywords: Transformational leadership; Structural validity, Multifactor Leadership Questionnaire; Confirmatory Factor Analysis
TL;DR: The effect of alternating shift work and day work on weight gain in Japanese male workers was compared to show the effect of either day or night work on body weight gain.
Abstract: Objective: This study compared the effect of alternating shift work and day work on weight gain in Japanese male workers.
Methods and Procedures: A longitudinal cohort study was conducted in day workers (n = 4,328) and alternating shift workers (n = 2,926) of a steel company who received annual health checkups over a 14-year period between 1991 and 2005. The association between the type of job schedule and weight gain was investigated using multivariate pooled logistic regression analyses. The endpoints in the study were either a 5, 7.5, or 10% increase in BMI during the period of observation, compared to the BMI at entry.
Results: The type of job schedule was significantly associated with all three BMI endpoints (5% increase in BMI; odds ratio (OR) for comparison between alternating shift workers and regular day workers, 1.14; 95% confidence interval (CI), 1.06–1.23): (7.5% increase in BMI; OR, 1.13; 95%CI, 1.03–1.24: 10% increase in BMI; OR, 1.13; 95%CI, 1.00–1.28). BMI at study entry was also positively associated with the 5, 7.5, and 10% increases in BMI during the study. On the other hand, age and drinking habits were negatively associated with 5, 7.5, and 10% increases in BMI.
Discussion: Our study revealed that alternating shift work was an independent risk factor for weight gain in male Japanese workers. Efficient health screening and regular checkups, combined with support to control unhealthy lifestyle factors, would be of considerable benefit for maintaining the health of Japanese shift workers.
TL;DR: The study provided new insights into the role of miRNAs and their target genes in the pathogenesis of fetal alcohol syndrome and caused mental retardation in their offspring.
Abstract: BACKGROUND: microRNAs (miRNAs) play an important role in development and are associated with birth defects. Data are scant on the role of miRNAs in birth defects arising from exposure to environmental factors such as alcohol. METHODS: In this study, we determined the expression levels of 509 mature miRNAs in fetal mouse brains with or without prenatal ethanol exposure using a miRNA microarray technique, verified by northern blot and PCR. Mouse embryos in culture were used to examine the effect of ethanol treatment on expression of the putative target genes of miR-10a (Hoxa1 and other Hox members) at mRNA and protein level. Open field and Morris water maze tests were also performed at post-natal day 35. RESULTS: Ethanol treatment induced major fetal teratogenesis in mice and caused mental retardation in their offspring, namely lower locomotor activity (P 1.5) in fetal brains with prenatal ethanol exposure, whereas miR-200a, miR-496, miR-296, miR-30e-5p, miR-362, miR-339, miR-29c and miR-154 were down-regulated (fold change <0.67). Both miR-10a and miR-10b were significantly up-regulated (P < 0.01) in brain after prenatal ethanol exposure. Ethanol treatment also caused major obstruction in the development of cultured embryos, with down-regulated Hoxa1. Co-incubation with folic acid blocked ethanol-induced teratogenesis, with up-regulated Hoxa1 and down-regulated miR-10a (P < 0.01). CONCLUSIONS: The study provided new insights into the role of miRNAs and their target genes in the pathogenesis of fetal alcohol syndrome.
TL;DR: It is found that multi-walled CNTs adjoining bone induce little local inflammatory reaction, show high bone-tissue compatibility, permit bone repair, become integrated into new bone, and accelerate bone formation stimulated by recombinant human bone morphogenetic protein-2 (rhBMP-2).
Abstract: Carbon nanotubes (CNTs) have been used in various fields as composites with other substances or alone to develop highly functional materials. CNTs hold great interest with respect to biomaterials, particularly those to be positioned in contact with bone such as prostheses for arthroplasty, plates or screws for fracture fixation, drug delivery systems, and scaffolding for bone regeneration. Accordingly, bone-tissue compatibility of CNTs and CNT influence on bone formation are important issues, but the effects of CNTs on bone have not been delineated. Here, it is found that multi-walled CNTs adjoining bone induce little local inflammatory reaction, show high bone-tissue compatibility, permit bone repair, become integrated into new bone, and accelerate bone formation stimulated by recombinant human bone morphogenetic protein-2 (rhBMP-2). This study provides an initial investigational basis for CNTs in biomaterials that are used adjacent to bone, including uses to promote bone regeneration. These findings should encourage development of clinical treatment modalities involving CNTs.
TL;DR: HNO donors are protective in the setting of heart failure in which NO donors have minimal impact and the therapeutic potential of HNO donors in the treatment of cardiovascular disease is highlighted.
TL;DR: Results indicate that a length-dependent formation of oligomers is an essential mechanism underlying neurodegeneration in polyQ-mediated disorders.
Abstract: Expanded polyglutamine (polyQ) repeats cause neurodegenerative disorders, but their cytotoxic structures remain to be elucidated. Although soluble polyQ oligomers have been proposed as a cytotoxic structure, the cytotoxicity of soluble polyQ oligomers, not inclusion bodies (IBs), has not been proven in living cells. To clarify the cytotoxicity of soluble polyQ oligomers, we carried our fluorescence resonance energy transfer (FRET) confocal microscopy and distinguished oligomers from monomers and IBs in a single living cell. FRET signals were detected when donor and acceptor fluorescent proteins were attached to the same side, not the opposite side, of polyQ repeats, which agrees with a parallel beta-sheet or a head-to-tail cylindrical beta-sheet model. These FRET signals disappeared in semi-intact cells, indicating that these polyQ oligomers are soluble. PolyQ monomers assembled into soluble oligomers in a length-dependent manner, which was followed by the formation of IBs. Notably, survival assay of neuronally differentiated cells revealed that cells with soluble oligomers died faster than those with IBs or monomers. These results indicate that a length-dependent formation of oligomers is an essential mechanism underlying neurodegeneration in polyQ-mediated disorders.
TL;DR: Findings reinforce the importance of innate immunity in the pathogenesis of different forms of aspergillosis in patients with severe asthma with fungal sensitization.
Abstract: Toll-like receptors (TLRs) are important components of innate immunity. We investigated the association between polymorphisms in the TLR2, TLR4, and TLR9 genes and susceptibility to noninvasive forms of pulmonary aspergillosis. A significant association was observed between allele G on Asp299Gly (TLR4) and chronic cavitary pulmonary aspergillosis (odds ratio [OR], 3.46; P =.003). Susceptibility to allergic bronchopulmonary aspergillosis was associated with allele C on T-1237C (TLR9) (OR, 2.49; P =. 043). No particular polymorphism was associated with severe asthma with fungal sensitization. These findings reinforce the importance of innate immunity in the pathogenesis of different forms of aspergillosis.