Lack of Association Between Haptoglobin Phenotype and Cystic Fibrosis Outcomes

Haptoglobin (Hp), a heme-Iron chelator, has different isoforms which are associated with variable tendency toward infections: Hp 1-1, Hp 2-1, and Hp 2-2. Cystic fibrosis (CF) outcomes are variable and influenced by genetic and environmental factors. The aim of this study was to determine whether Hp phenotype influenced disease severity in CF. One hundred forty-two CF patients from two centers were analyzed for Haptoglobin phenotype using gel electrophoresis of hemoglobin enriched serum. Clinical and microbiological data including bacterial colonization status, lung function, presence of CF-related diabetes and liver disease, rate of exacerbation, and mortality were compared between Hp phenotype groups. We found a trend toward less mucoid PA among Hp 2-2 (20.4 %) compared with Hp 1-1 and Hp 2-1 individuals (33.3 %), p = 0.317. Hp 2-2 individuals also had less antibiotic courses, and lower inflammatory markers without statistical significance. Haptoglobin phenotype is unlikely to be an important modifier of CF phenotype.

Measuring the sustainability of a national economy. The application of three measures of sustainability to Ireland

An assessment of the sustainability of the Irish economy has been carried out using three methodologies, enabling comparison and evaluation of the advantages and disadvantages of each, and potential synergies among them. The three measures chosen were economy-wide Material Flow Analysis (MFA), environmentally extended input-output (EE-IO) analysis and the Ecological Footprint (EF). The research aims to assess the sustainability of the Irish economy using these methods and to draw conclusions on their effectiveness in policy making both individually and in combination. A theoretical description discusses the methods and their respective advantages and disadvantages and sets out a rationale for their combined application. The application of the methods in combination has provided insights into measuring the sustainability of a national economy and generated new knowledge on the collective application of these methods. The limitations of the research are acknowledged and opportunities to address these and build on and extend the research are identified. Building on previous research, it is concluded that a complete picture of sustainability cannot be provided by a single method and/or indicator.

No clear evidence of an association between plasma concentrations of n-3 long-chain polyunsaturated fatty acids and depressed mood in a non-clinical population

Previous research suggests that low n-3 long-chain polyunsaturated fatty acid (n-3PUFA) status is associated with higher levels of depression in clinical populations. This analysis aimed to investigate the relationship between depressed mood and n-3PUFA status in a non-clinical population. The analysis was conducted on data collected as part of a large randomized controlled trial investigating the impact of n-3PUFA supplementation on depressed mood in a community-based population. On entry into the trial, data on depressed mood were collected using the Depression, Anxiety and Stress Scales (DASS) and the Beck Depression Inventory (BDI). Plasma concentrations of various n-3PUFAs and n-6 long-chain polyunsaturated fatty acids (n-6PUFAs) were obtained from fasting venous blood samples, and various demographics were also measured. Using regression, there was no evidence of an association between either measure of depressed mood and any of the measures of n-3PUFA status or of n-6PUFA: n-3PUFA ratios. Clear associations were also not found when demographic factors were included in the analyses. These findings suggest that n-3PUFAs may not have a role in the aetiology of minor depression. This is also consistent with the results of other studies that have not demonstrated an association between depressed mood and n-3PUFA status in non-clinical populations and epidemiological studies that have not demonstrated an association between depressed mood and n-3PUFA intake in these populations. (C) 2008 Elsevier Ltd. All rights reserved.

A review and psychometric evaluation of pregnancy-specific stress measures

Considerable evidence has accumulated on the association between pregnancy-specific stress and adverse birth outcomes with an increasing number of measures of pregnancy-specific stress being developed internationally. However, the introduction of these measures has not always been theoretically or psychometrically grounded, resulting in questions about the quality and direction of such research. This review summarizes evidence on the reliability and validity of pregnancy-specific stress measures identified between 1980 and October 2010. Fifteen pregnancy-specific stress measures were identified. Cronbach’s alpha coefficient ranged from 0.51–0.96 and predictive validity data on preterm birth were reported for five measures. Convergent validity data suggest that pregnancy-specific stress is related to, but distinct from, global stress. Findings from this review consolidate current knowledge on pregnancy-specific stress as a consistent predictor of premature birth. This review also advances awareness of the range of measures of pregnancy-specific stress and documents their strengths and limitations based on published reliability and validity data. Careful consideration needs to be given as to which measures to use in future research to maximize the development of stress theory in pregnancy and appropriate interventions for women who experience stress in pregnancy. An international, strategic collaboration is recommended to advance knowledge in this area of study.

Genome-wide association study to identify genetic determinants of severe asthma

BACKGROUND: The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. OBJECTIVE: To identify common genetic variants affecting susceptibility to severe asthma. METHODS: A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480?889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. RESULTS: An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10((-8)) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10((-8)) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. CONCLUSIONS: The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.

The Association of Skin-Intrinsic Fluorescence With Type 1 Diabetes Complications in the DCCT/EDIC Study

OBJECTIVESTo determine whether skin-intrinsic fluorescence (SIF) is associated with long-term complications of type 1 diabetes (T1D) and, if so, whether it is independent of chronic glycemic exposure and previous intensive therapy.RESEARCH DESIGN AND METHODSWe studied 1,185 (92%) of 1,289 active Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) participants from 2010 to 2011. SIF was determined using a fluorescence spectrometer and related cross-sectionally to recently determined measures of retinopathy (stereo fundus photography), cardiac autonomic neuropathy (CAN; R-R interval), confirmed clinical neuropathy, nephropathy (albumin excretion rate [AER]), and coronary artery calcification (CAC).RESULTSOverall, moderately strong associations were seen with all complications, before adjustment for mean HbA1c over time, which rendered these associations nonsignificant with the exception of sustained AER >30 mg/24 h and CAC, which were largely unaffected by adjustment. However, when examined within the former DCCT treatment group, associations were generally weaker in the intensive group and nonsignificant after adjustment, while in the conventional group, associations remained significant for CAN, sustained AER >30 mg/24 h, and CAC even after mean HbA1c adjustment.CONCLUSIONSSIF is associated with T1D complications in DCCT\EDIC. Much of this association appears to be related to historical glycemic exposure, particularly in the previously intensively treated participants, in whom adjustment for HbA1c eliminates statistical significance.

Inverse Association Between Gluteofemoral Obesity and Risk of Barrett's Esophagus in a Pooled Analysis

BACKGROUND & AIMS: Gluteofemoral obesity (determined by measurement of subcutaneous fat in hip and thigh regions) could reduce risks of cardiovascular and diabetic disorders associated with abdominal obesity. We evaluated whether gluteofemoral obesity also reduces risk of Barrett's esophagus (BE), a premalignant lesion associated with abdominal obesity.

METHODS: We collected data from non-Hispanic white participants in 8 studies in the Barrett's and Esophageal Adenocarcinoma Consortium. We compared measures of hip circumference (as a proxy for gluteofemoral obesity) from cases of BE (n=1559) separately with 2 control groups: 2557 population-based controls and 2064 individuals with gastroesophageal reflux disease (GERD controls). Study-specific odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using individual participant data and multivariable logistic regression and combined using random effects meta-analysis.

RESULTS: We found an inverse relationship between hip circumference and BE (OR per 5 cm increase, 0.88; 95% CI, 0.81-0.96), compared with population-based controls in a multivariable model that included waist circumference. This association was not observed in models that did not include waist circumference. Similar results were observed in analyses stratified by frequency of GERD symptoms. The inverse association with hip circumference was only statistically significant among men (vs population-based controls: OR, 0.85; 95% CI, 0.76-0.96 for men; OR, 0.93; 95% CI, 0.74-1.16 for women). For men, within each category of waist circumference, a larger hip circumference was associated with decreased risk of BE. Increasing waist circumference was associated with increased risk of BE in the mutually adjusted population-based and GERD control models.

CONCLUSIONS: Although abdominal obesity is associated with increased risk of BE, there is an inverse association between gluteofemoral obesity and BE, particularly among men.

Investigating the cost Performance of UK Credit Unions using Radial and Non-Radial Efficiency Measures

This paper examines the relative efficiency of UK credit unions. Radial and non-radial measures of input cost efficiency plus associated scale efficiency measures are computed for a selection of input output specifications. Both measures highlighted that UK credit unions have considerable scope for efficiency gains. It was mooted that the documented high levels of inefficiency may be indicative of the fact that credit unions, based on clearly defined and non-overlapping common bonds, are not in competition with each other for market share. Credit unions were also highlighted as suffering from a considerable degree of scale inefficiency with the majority of scale inefficient credit unions subject to decreasing returns to scale. The latter aspect highlights that the UK Government's goal of larger credit unions must be accompanied by greater regulatory freedom if inefficiency is to be avoided. One of the advantages of computing non-radial measures is that an insight into potential over- or under-expenditure on specific inputs can be obtained through a comparison of the non-radial measure of efficiency with the associated radial measure. Two interesting findings emerged, the first that UK credit unions over-spend on dividend payments and the second that they under-spend on labour costs.

Depressed mood and dietary fish intake: Direct relationship or indirect relationship as a result of diet and lifestyle?

Previous studies have suggested an association between depressed mood and the dietary intake of fish. In all cases, however, dietary fish intake has been considered at the exclusion of all other aspects of the diet. This analysis investigates associations between depressed mood and dietary fish intake, while also concurrently investigating intake of a number of other dietary components. The analysis is conducted on data from 10,602 men from Northern Ireland and France screened for inclusion into the PRIME cohort study. Depressed mood was assessed using a self-report questionnaire based on the Welsh Pure Depression sub-scale of the Minnesota Multiphasic Personality Inventory, diet was assessed using a Food Frequency Questionnaire, and limited demographics were also measured. Using regression, depressed mood is initially inversely associated with dietary fish intake. On inclusion of all other dietary variables, the strength of this relationship reduces but remains, and significant associations with a number of other foods are also found. On additional inclusion of all demographic variables, the strength of the above relationships again reduces, and associations with various measures of socio-economic status and education are also significant. These findings suggest that depressed mood is associated with fish intake both directly, and indirectly as part of a diet that is associated with depression and as part of a lifestyle that is associated with depression. Additional support for these conclusions is also provided in the pattern of associations between depressed mood and diet in the two countries. The relative contributions of fish intake to depressed mood both directly and indirectly are yet to be determined. However, while diet is not measured and until lifestyle can be adequately measured, the potential roles of diet and lifestyle in the association between depressed mood and dietary fish intake should not be ignored.

Insight into association reactions on metal surfaces: Density-functional theory studies of hydrogenation reactions on Rh(111)

Hydrogenation reaction, as one of the simplest association reactions on surfaces, is of great importance both scientifically and technologically. They are essential steps in many industrial processes in heterogeneous catalysis, such as ammonia synthesis (N-2+3H(2)-->2NH(3)). Many issues in hydrogenation reactions remain largely elusive. In this work, the NHx (x=0,1,2) hydrogenation reactions (N+H-->NH, NH+H-->NH2 and NH2+H-->NH3) on Rh(111) are used as a model system to study the hydrogenation reactions on metal surfaces in general using density-functional theory. In addition, C and O hydrogenation (C+H-->CH and O+H-->OH) and several oxygenation reactions, i.e., C+O, N+O, O+O reactions, are also calculated in order to provide a further understanding of the barrier of association reactions. The reaction pathways and the barriers of all these reactions are determined and reported. For the C, N, NH, and O hydrogenation reactions, it is found that there is a linear relationship between the barrier and the valency of R (R=C, N, NH, and O). Detailed analyses are carried out to rationalize the barriers of the reactions, which shows that: (i) The interaction energy between two reactants in the transition state plays an important role in determining the trend in the barriers; (ii) there are two major components in the interaction energy: The bonding competition and the direct Pauli repulsion; and (iii) the Pauli repulsion effect is responsible for the linear valency-barrier trend in the C, N, NH, and O hydrogenation reactions. For the NH2+H reaction, which is different from other hydrogenation reactions studied, the energy cost of the NH2 activation from the IS to the TS is the main part of the barrier. The potential energy surface of the NH2 on metal surfaces is thus crucial to the barrier of NH2+H reaction. Three important factors that can affect the barrier of association reactions are generalized: (i) The bonding competition effect; (ii) the local charge densities of the reactants along the reaction direction; and (iii) the potential energy surface of the reactants on the surface. The lowest energy pathway for a surface association reaction should correspond to the one with the best compromise of these three factors. (C) 2003 American Institute of Physics.

Homocysteine, Methylenetetrahydrofolate Reductase C677T Polymorphism, and Risk of Retnal Vein Occlusion: A Meta-analysis

Objective: To assess the role of plasma total homocysteine (tHcy) concentrations and homozygosity for the thermolabile variant of the methylenetetrahydrofolate reductase (MTHFR) C677T gene as risk factors for retinal vascular occlusive disease.

Design: Retinal vein occlusion (RVO) is an important cause of vision loss. Early meta-analyses showed that tHcy was associated with an increased risk of RVO, but a significant number of new studies have been published. Participants and/or Controls: RVO patients and controls.

Methods: Data sources included MEDLINE, Web of Science, and PubMed searches and searching reference lists of relevant articles and reviews. Reviewers searched the databases, selected the studies, and then extracted data. Results were pooled quantitatively using meta-analytic methods.

Main Outcome Measures: tHcy concentrations and MTHFR genotype.

Results: There were 25 case-control studies for tHcy (1533 cases and 1708 controls) and 18 case-control studies for MTHFR (1082 cases and 4706 controls). The mean tHcy was on average 2.8 mol/L (95% confidence
interval [CI], 1.8 –3.7) greater in the RVO cases compared with controls, but there was evidence of between-study heterogeneity (P0.001, I2 93%). There was funnel plot asymmetry suggesting publication bias. There was no evidence of association between homozygosity for the MTHFR C677T genotype and RVO (odds ratio [OR] 1.20; 95% CI, 0.84–1.71), but again marked heterogeneity (P 0.004, I2 53%) was observed.

Conclusions: There was some evidence that elevated tHcy was associated with RVO, but not homozygosity for the MTHFR C677T genotype. Both analyses should be interpreted cautiously because of marked heterogeneity between the study estimates and possible effect of publication bias on the tHcy findings.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The Association Between Childhood Trauma and Memory Functioning in Schizophrenia

Objective: Both neurocognitive impairments and a history of childhood abuse are highly prevalent in patients with schizophrenia. Childhood trauma has been associated with memory impairment as well as hippocampal volume reduction in adult survivors. The aim of the following study was to examine the contribution of childhood adversity to verbal memory functioning in people with schizophrenia. Methods: Eighty-five outpatients with a Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnosis of chronic schizophrenia were separated into 2 groups on the basis of self-reports of childhood trauma. Performance on measures of episodic narrative memory, list learning, and working memory was then compared using multivariate analysis of covariance. Results: Thirty-eight (45%) participants reported moderate to severe levels of childhood adversity, while 47 (55%) reported no or low levels of childhood adversity. After controlling for premorbid IQ and current depressive symptoms, the childhood trauma group had significantly poorer working memory and episodic narrative memory. However, list learning was similar between groups. Conclusion: Childhood trauma is an important variable that can contribute to specific ongoing memory impairments in schizophrenia.

Responses of calves to acute stress: Individual consistency and relations between behavioral and physiological measures

The present study examined the consistency over time of individual differences in behavioral and physiological responsiveness of calves to intuitively alarming test situations as well as the relationships between behavioral and physiological measures. Twenty Holstein Friesian heifer calves were individually subjected to the same series of two behavioral and two hypothalamo-pituitary-adrenocortical (HPA) axis reactivity tests at 3, 13 and 26 weeks of age. Novel environment (open field, OF) and novel object (NO) tests involved measurement of behavioral, plasma cortisol and heart rate responses. Plasma ACTH and/or cortisol response profiles were determined after administration of exogenous CRH and ACTH, respectively, in the HPA axis reactivity tests. Principal component analysis (PCA) was used to condense correlated measures within ages into principal components reflecting independent dimensions underlying the calves' reactivity. Cortisol responses to the OF and NO tests were positively associated with the latency to contact and negatively related to the time spent in contact with the NO. Individual differences in scores of a principal component summarizing this pattern of inter-correlations, as well as differences in separate measures of adrenocortical and behavioral reactivity in the OF and NO tests proved highly consistent over time. The cardiac response to confinement in a start box prior to the OF test was positively associated with the cortisol responses to the OF and NO tests at 26 weeks of age. HPA axis reactivity to ACTH or CRH was unrelated to adrenocortical and behavioral responses to novelty. These findings strongly suggest that the responsiveness of calves was mediated by stable individual characteristics. Correlated adrenocortical and behavioral responses to novelty may reflect underlying fearfulness, defining the individual's susceptibility to the elicitation of fear. Other independent characteristics mediating reactivity may include activity or coping style (related to locomotion) and underlying sociality (associated with vocalization). (c) 2005 Elsevier Inc. All rights reserved.

Orotate complexes of rhodium(I) and iridium(I): effect of coligand, counter ion, and solvent of crystallisation on association via complementary hydrogen bonding

The new complexes [NEt3H][M(HL)(cod)] (M = Rh 1 or Ir 2; H3L = 2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid, erotic acid; cod = cycloocta-1,5-diene) have been prepared by the reaction between [M2Cl2(cod)(2)] and erotic acid in dichloromethane in the presence of Ag2O and NEt3. They crystallise as dichloromethane adducts 1 . CH2Cl2 and 2 . CH2Cl2 from dichloromethane-hexane solutions. These isomorphous structures contain doubly hydrogen-bonded dimers, with additional hydrogen bonding to NEt3H+ cations and bridging CH2Cl2 molecules to form tapes. The use of (NBu4OH)-O-n instead of NEt3 gave the related complex [NBu4n][Rh(HL)(cod)] 1' which has an innocent cation not capable of forming strong hydrogen bonds and in contrast to 1 exists as discrete doubly hydrogen-bonded dimers. Complex 1' cocrystallises with 2,6-diaminopyridine (dap) via complementary triple hydrogen bonds to give [NBu4n][Rh(HL)(cod)]. dap . CH2Cl2 3. Complex 3 exhibits an extended sheet structure of associated [2 + 2] units, with layers of NBu4n, cations separating the sheets. These structural data together with those reported previously for platinum orotate complexes suggest that the steric requirements of the other ligands co-ordinated to the metal are important in influencing their hydrogen-bonding abilities. The solvent of crystallisation, the hydrogen-bonding propensity of the coligand and the nature of the counter ion also determine the type of association in the solid state.