Inhibition of platelet aggregation by omega-3 polyunsaturated fatty acids is gender specific — redefining platelet response to fish oils

Existence of gender differences in cardiovascular disease (CVD) following long-chain omega-3 polyunsaturated fatty acid (LCn-3 PUFA) supplementation have suggested that sex hormones play a role in cardio-protection. The objective of this study was to determine gender specific responses in the efficacy of LCn-3 PUFA to inhibit platelet aggregation in vitro. Blood was analyzed for collagen-induced platelet aggregation following pre-incubation with LCn-3 PUFA in healthy adults (n=42). Eicosapentaenoic acid (EPA) was significantly more effective in reducing platelet aggregation compared with docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). When grouped by gender, this differential pattern was followed in males only. In females, DHA, DPA and EPA were all equally effective. Between group analyses (LCn-3 PUFA vs. gender) showed that both DHA and DPA were significantly less effective in males compared with females. EPA was equally effective in reducing platelet aggregation in both groups. These findings show that significant gender differences exist in platelet aggregation in response to various LCn-3 PUFA treatments.

Multi-type maltreatment : relationships between familial characteristics, maltreatment and adjustment of children and adults

This thesis examines the nature, extent and impact of multiple forms of maltreatment (multi-type maltreatment) from within a developmental victimological framework. The interrelationships between sexual abuse, physical abuse, psychological maltreatment, neglect, and witnessing family violence are assessed. The role of family variables in predicting maltreatment and the relative contribution of child maltreatment and family variables to adjustment are evaluated. Risk factors for multi-type maltreatment, and the relationship between multi-type maltreatment and adjustment are explored. The major theories of child development are reviewed. As well as exploring the relevance of developmental theories to understanding the impact of child maltreatment, factors influencing the emergence of child psychopathology are reviewed from a developmental psychopathology perspective. Ecological and developmental perspectives on how child maltreatment translates into the behavioural and emotional adjustment problems of children are integrated in the Child Maltreatment: Risk and Protection Model. After exploring some of the relevant conceptual issues, the literature on the prevalence and impact of each maltreatment type is reviewed, and the literature on multi-type maltreatment critiqued. Methodological and ethical concerns with the conduct of research in the field of child maltreatment using direct assessment of children led to the need for an instrument to assess parent perceptions of each of the types of abuse and neglect, as well as adult retrospective reports. Data are presented from two cross-sectional questionnaire-based studies using the Parent and Adult versions of the Family and Life Experiences Questionnaire which was designed to assess perceptions of children's experiences of sexual abuse, physical abuse, psychological maltreatment, neglect and witnessing family violence. Problems with the isolated focus of research on single forms of child maltreatment are addressed by the inclusion of each of these forms of child maltreatment within a single research design. Respondents for both studies were volunteers recruited from counselling agencies, medical, community health, child care and fitness centres and a first year psychology course. Parents (N=50) described their perceptions of primary school children's family characteristics, experiences of maltreatment and adjustment. Children's behavioural adjustment (internalising and externalising), sexual behaviours, emotions, self-esteem, gender identity, family adaptability and cohesion, parental traditionality, parental sexual punitiveness, interparental relationship satisfaction, and demographic characteristics are assessed in the study of Parents' perceptions. A large degree of overlap between the different types of abuse and neglect was found, with a high proportion of parents describing children's experiences of multiple forms of child maltreatment. Using both maltreatment and family characteristics to predict internalising behaviour problems, neglect and family cohesion were the only unique predictors. Family adaptability and cohesion were the only unique predictors of externalising behaviour problems. Physical and sexual abuse were not predicted from family characteristics; neglect was predicted, but no variables provided unique prediction. Unique predictors of psychological maltreatment were family cohesion, parental sexual punitiveness and divorce. Divorce was the only variable with significant unique prediction of the child witnessing family violence. Family background and family functioning were found to predict some forms of maltreatment, but to also be important factors mediating the adjustment of children, independent of maltreatment. The results are interpreted within an ecological framework, integrating risk factors for maltreatment with experiences of abuse and neglect and subsequent adjustment in childhood. Retrospective reports of adults' (N=175) own childhood family characteristics, experiences of maltreatment, and reports of their current adjustment are also studied. Included with the adult version of the FLEQ were the Trauma Symptom Checklist-40, Rosenberg's Self-esteem Scale, and the Family and Adaptability and Cohesion Evaluation Scale-II. Similar results were found in the in the Adult Study. As hypothesised, adult retrospective reports of the five different types of child maltreatment were found to be highly intercorrelated. Family characteristics predicted maltreatment and adjustment scores and discriminated between single and multi-type maltreatment. Maltreatment scores also predicted adult adjustment. As the number of maltreatment types increased, there was an increase in the number of adjustment problems reported. Alternate hypotheses regarding the possible operation of mediating and moderating processes in the relationships between family characteristics, maltreatment and the adjustment of adults were assessed. Finally, the results of these investigations are discussed and interpreted in the light of extant findings previously reviewed. Data from the two major empirical studies are used to demonstrate the overlap between different child maltreatment categories, and the extent and impact of multi-type maltreatment. The results show that children are vulnerable to more than one type of maltreatment. Individuals who experience a number of different forms of maltreatment had greater adjustment problems than those experiencing only one or two different types of abuse or neglect. Dysfunctional families place children at risk of child maltreatment. Negative family characteristics lead to adjustment problems in children and adults. The type of maltreatment having the most damaging effect on children was neglect, and in the long-term, sexual abuse. A multi-dimensional approach to prevention and intervention needs to be adopted, based on the co-morbidity of maltreatment types, and the likelihood of children experiencing further abuse or neglect of a different type. Dysfunctional family dynamics which place children at risk of multi-type maltreatment, and mediate the effects of maltreatment on adjustment, need to be specifically targeted with support and family intervention strategies. Risk-assessment measures used by Child Protection workers must include adequate knowledge of the inter-relationships between maltreatment types, and the particularly negative impact on adjustment of experiencing many forms of abuse or neglect. Suggestions for future clinical and research work in the area of child maltreatment are developed. The importance of assessing all forms of maltreatment when examining the relationships of maltreatment to adjustment is emphasised. It is recommended that prevention and intervention strategies acknowledge the interrelationships between maltreatment types.

Antihypertensive treatments obscure familial contributions to blood pressure variation

The linkage and association between inherent blood pressure and underlying genotype is potentially confounded by antihypertensive treatment. We estimated blood pressure variance components (genetic, shared environmental, individual-specific) in 767 adult volunteer families by using a variety of approaches to adjusting blood pressure of the 244 subjects (8.2%) receiving antihypertensive medications. The additive genetic component of variance for systolic pressure was 73.9 mm Hg(2) (SE, 8.8) when measured pressures (adjusted for age by gender within each generation) were used but fell to 61.4 mm Hg(2) (SE, 8.0) when treated subjects were excluded. When the relevant 95th percentile values were substituted for treated systolic pressures, the additive genetic component was 81.9 mm Hg(2) (SE, 9.5), but individual adjustments in systolic pressure ranged from -53.5 mm Hg to +64.5 mm Hg (mean, +17.2 mm Hg). Instead, when 10 mm Hg was added to treated systolic pressure, the additive genetic component rose to 86.6 mm Hg(2) (SE, 10.1). Similar changes were seen in the shared environment component of variance for systolic pressure and for the combined genetic and shared environmental (ie, familial) components of diastolic pressure. There was little change in the individual-specific variance component across any of the methods. Therefore, treated subjects contribute important information to the familial components of blood pressure variance. This information is lost if treated subjects are excluded and obscured by treatment effects if unadjusted measured pressures are used. Adding back an appropriate increment of pressure restores familial components, more closely reflects the pretreatment values, and should increase the power of genomic linkage and linkage disequilibrium analyses.

Familial and genomic analyses of postural changes in systolic and diastolic blood pressure

The physiological adaptation to the erect posture involves integrated neural and cardiovascular responses that might be determined by genetic factors. We examined the familial- and individual-specific components of variance for postural changes in systolic and diastolic blood pressure in 767 volunteer nuclear adult families from the Victorian Family Heart Study. In 274 adult sibling pairs, we made a genome-wide scan using 400 markers for quantitative trait loci linked with the postural changes in systolic and diastolic pressures. Overall, systolic pressure did not change on standing, but there was considerable variation in this phenotype (SD=8.1 mm Hg). Familial analyses revealed that 25% of the variance of change in systolic pressure was attributable to genetic factors. In contrast, diastolic pressure increased by 6.3 mm Hg (SD=7.0 mm Hg) on standing and there was no evidence of contributory genetic factors. Multipoint quantitative genome linkage mapping suggested evidence (Z=3.2) of linkage of the postural change in systolic pressure to chromosome 12 but found no genome-wide evidence of linkage for the change in diastolic pressure. These findings suggest that genetic factors determine whether systolic pressure decreases or increases when one stands, possibly as the result of unidentified alleles on chromosome 12. The genetics of postural changes in systolic blood pressure might reflect the general buffering function of the baroreflex; thereby, the predisposition to sudden decreases or increases in systolic pressure might cause postural hypotension or vessel wall disruption, respectively.

Construction of aggregation functions from data using linear programming

This article examines the construction of aggregation functions from data by minimizing the least absolute deviation criterion. We formulate various instances of such problems as linear programming problems. We consider the cases in which the data are provided as intervals, and the outputs ordering needs to be preserved, and show that linear programming formulation is valid for such cases. This feature is very valuable in practice, since the standard simplex method can be used.

Aggregation functions based on penalties

This article studies a large class of averaging aggregation functions based on minimizing a distance from the vector of inputs, or equivalently, minimizing a penalty imposed for deviations of individual inputs from the aggregated value. We provide a systematization of various types of penalty based aggregation functions, and show how many special cases arise as the result. We show how new aggregation functions can be constructed either analytically or numerically and provide many examples. We establish connection with the maximum likelihood principle, and present tools for averaging experimental noisy data with distinct noise distributions.

On Lipschitz properties of generated aggregation functions

This article discusses Lipschitz properties of generated aggregation functions. Such generated functions include triangular norms and conorms, quasi-arithmetic means, uninorms, nullnorms and continuous generated functions with a neutral element. The Lipschitz property guarantees stability of aggregation operations with respect to input inaccuracies, and is important for applications. We provide verifiable sufficient conditions to determine when a generated aggregation function holds the k-Lipschitz property, and calculate the Lipschitz constants of power means. We also establish sufficient conditions which guarantee that a generated aggregation function is not Lipschitz. We found the only 1-Lipschitz generated function with a neutral element e ∈]0, 1[.

A microfluidics device to monitor platelet aggregation dynamics in response to strain rate micro-gradients in flowing blood

This paper reports the development of a platform technology for measuring platelet function and aggregation based on localized strain rate micro-gradients. Recent experimental findings within our laboratories have identified a key role for strain rate micro-gradients in focally triggering initial recruitment and subsequent aggregation of discoid platelets at sites of blood vessel injury. We present the design justification, hydrodynamic characterization and experimental validation of a microfluidic device incorporating contraction–expansion geometries that generate strain rate conditions mimicking the effects of pathological changes in blood vessel geometry. Blood perfusion through this device supports our published findings of both in vivo and in vitro platelet aggregation and confirms a critical requirement for the coupling of blood flow acceleration to downstream deceleration for the initiation and stabilization of platelet aggregation, in the absence of soluble platelet agonists. The microfluidics platform presented will facilitate the detailed analysis of the effects of hemodynamic parameters on the rate and extent of platelet aggregation and will be a useful tool to elucidate the hemodynamic and platelet mechano-transduction mechanisms, underlying this shear-dependent process.

Gender-specific inhibition of platelet aggregation following omega-3 fatty acid supplementation

Background and Aims : Increased platelet aggregation is a major risk factor for heart attacks, stroke and thrombosis. Long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA; eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) reduce platelet aggregation; however studies in the published literature involving EPA and/or DHA supplementation have yielded equivocal results. Recent in vitro studies have demonstrated that inhibition of platelet aggregation by LCn-3PUFA is gender specific. We examined the acute effects of dietary supplementation with EPA or DHA rich oils on platelet aggregation in healthy male and females.

Methods and Results : A blinded placebo controlled trial involving 15 male and 15 female subjects. Platelet aggregation was measured at 0, 2, 5 and 24 h post-supplementation with a single dose of either a placebo or EPA or DHA rich oil capsules. The relationship between LCn-3PUFA and platelet activity at each time point was examined according to gender vs. treatment. EPA was significantly the most effective in reducing platelet aggregation in males at 2, 5 and 24 h post-supplementation (−11%, −10.6%, −20.5% respectively) whereas DHA was not effective relative to placebo. In contrast, in females, DHA significantly reduced platelet aggregation at 24 h (−13.7%) while EPA was not effective. An inverse relationship between testosterone levels and platelet aggregation following EPA supplementation was observed.

Conclusion : Interactions between sex hormones and omega-3 fatty acids exist to differentially reduce platelet aggregation. For healthy individuals, males may benefit more from EPA supplementation while females are more responsive to DHA.

Aggregation, ageing and transport properties of surface modified fumed silica dispersions

We have investigated the aggregation, ageing and transport properties of surface modified silica dispersions in DMSO by photon correlation spectroscopy and conductivity measurements. The surface modification introduces Li+-ions that dissociate in the dispersion creating a single Li+-ion conducting electrolyte. We show that the surface modification changes the aggregation and ageing properties of the material. There is a pronounced ageing observed for the modified silica dispersions. At high concentrations of fumed silica a gel state is found, which in the case of the surface modified silica is a very weak gel that can be rejuvenated by ultrasonic treatment. The key parameter controlling the aggregation in this system is hydrogen bonding and the surface modification results in a very low number of sites for hydrogen bonding. In addition there is a contribution from repulsive electrostatic interactions in the surface modified silica dispersions due to the highly charged surfaces of these particles. Furthermore, the Li+-ion diffusion, at low silica concentration, is three orders of magnitude faster than that of the silica particles and in the gel state the silica particles are immobile. We also find that the Li+-ion diffusion is virtually independent of the silica concentration in the dispersions.

Generalized Bonferroni mean operators in multi-criteria aggregation

In this paper we provide a systematic investigation of a family of composed aggregation functions which generalize the Bonferroni mean. Such extensions of the Bonferroni mean are capable of modeling the concepts of hard and soft partial conjunction and disjunction as well as that of k-tolerance and k-intolerance. There are several interesting special cases with quite an intuitive interpretation for application.

Optimization and aggregation functions

In this work we will look at connections between aggregation functions and optimization. There are two such connections: 1) aggregation functions are used to transform a multiobjective optimization problem into a single objective problem by aggregating several criteria into one, and 2) construction of aggregation functions often involves an optimization problem.

Use of aggregation functions in decision making

A key component of many decision making processes is the aggregation step, whereby a set of numbers is summarised with a single representative value. This research showed that aggregation functions can provide a mathematical formalism to deal with issues like vagueness and uncertainty, which arise naturally in various decision contexts.