Tailoring Consumer Resources to Enhance Self-Care in Chronic Heart Failure

Background Chronic heart failure (CHF) is associated with high hospitalisation and mortality rates and debilitating symptoms. In an effort to reduce hospitalisations and improve symptoms individuals must be supported in managing their condition. Patients who can effectively self-manage their symptoms through lifestyle modification and adherence to complex medication regimens will experience less hospitalisations and other adverse events. Aim The purpose of this paper is to explain how providing evidence-based information, using patient education resources, can support self-care. Discussion Self-care relates to the activities that individuals engage in relation to health seeking behaviours. Supporting self-care practices through tailored and relevant information can provide patients with resources and advice on strategies to manage their condition. Evidence-based approaches to improve adherence to self-care practices in patients with heart failure are not often reported. Low health literacy can result in poor understanding of the information about CHF and is related to adverse health outcomes. Also a lack of knowledge can lead to non-adherence with self-care practices such as following fluid restriction, low sodium diet and daily weighing routines. However these issues need to be addressed to improve self-management skills. Outcome Recently the Heart Foundation CHF consumer resource was updated based on evidence-based national clinical guidelines. The aim of this resource is to help consumers improve understanding of the disease, reduce uncertainty and anxiety about what to do when symptoms appear, encourage discussions with local doctors, and build confidence in self-care management. Conclusion Evidence-based CHF patient education resources promote self-care practices and early detection of symptom change that may reduce hospitalisations and improve the quality of life for people with CHF.

An evaluation of alternative media for pebble matrix filtration using clay balls and recycled crushed glass

Protecting slow sand filters (SSFs) from high-turbidity waters by pretreatment using pebble matrix filtration (PMF) has previously been studied in the laboratory at University College London, followed by pilot field trials in Papua New Guinea and Serbia. The first full-scale PMF plant was completed at a water-treatment plant in Sri Lanka in 2008, and during its construction, problems were encountered in sourcing the required size of pebbles and sand as filter media. Because sourcing of uniform-sized pebbles may be problematic in many countries, the performance of alternative media has been investigated for the sustainability of the PMF system. Hand-formed clay balls made at a 100-yearold brick factory in the United Kingdom appear to have satisfied the role of pebbles, and a laboratory filter column was operated by using these clay balls together with recycled crushed glass as an alternative to sand media in the PMF. Results showed that in countries where uniform-sized pebbles are difficult to obtain, clay balls are an effective and feasible alternative to natural pebbles. Also, recycled crushed glass performed as well as or better than silica sand as an alternative fine media in the clarification process, although cleaning by drainage was more effective with sand media. In the tested filtration velocity range of ð0:72–1:33Þ m=h and inlet turbidity range of (78–589) NTU, both sand and glass produced above 95% removal efficiencies. The head loss development during clogging was about 30% higher in sand than in glass media.

The link between belongingness and depressive symptoms: An exploration in the workplace interpersonal context

Interpersonal factors are crucial to a deepened understanding of depression. Belongingness, also referred to as connectedness, has been established as a strong risk/protective factor for depressive symptoms. To elucidate this link it may be beneficial to investigate the relative importance of specific psychosocial contexts as belongingness foci. Here we investigate the construct of workplace belongingness. Employees at a disability services organisation (N = 125) completed measures of depressive symptoms, anxiety symptoms, workplace belongingness and organisational commitment. Psychometric analyses, including Horn's parallel analyses, indicate that workplace belongingness is a unitary, robust and measurable construct. Correlational data indicate a substantial relationship with depressive symptoms (r = −.54) and anxiety symptoms (r = −.39). The difference between these correlations was statistically significant, supporting the particular importance of belongingness cognitions to the etiology of depression. Multiple regression analyses support the hypothesis that workplace belongingness mediates the relationship between affective organisational commitment and depressive symptoms. It is likely that workplaces have the potential to foster environments that are intrinsically less depressogenic by facilitating workplace belongingness. From a clinical perspective, cognitions regarding the workplace psychosocial context appear to be highly salient to individual psychological health, and hence warrant substantial attention.

Attachment, fear of intimacy and differentiation of self among clients in substance disorder treatment facilities

Attachment, fear of intimacy and differentiation of self were examined by means of self-report questionnaires in 158 volunteers, including 99 clients enrolled in addiction treatment programs. As expected, clients (who were undergoing treatment for alcoholism, heroin addiction, amphetamine/cocaine addiction or cannabis abuse) reported higher levels of insecure attachment and fear of intimacy, and lower levels of secure attachment and differentiation of self, compared to controls. Insecure attachment, high fear of intimacy and low self-differentiation appear to characterize clients enrolled in addiction treatment programs. Such characteristics may reflect a predisposition to substance problems, an effect of chronic substance problems, or conceivably both.

Is adiponectin implicated in venous thromboembolism?

In summary, these results imply that the relationship of adiponectin with lipoproteins is more complex than previously predicted using other methods of lipoprotein fractionation. Higher correlation of adiponectin was shown with large lipoprotein particle size, independent of the apolipoprotein content. Given the small population studied, we could not assess the influence of mild risk factors for venous thrombosis, such as obesity, on the analysis of the results. Thus, we can only state that adiponectin levels appear not to be a strong risk factor for VTE. It is possible that adiponectin deficiency may contribute indirectly to the etiology of VTE by enhancing the inflammatory state. © 2006 International Society on Thrombosis and Haemostasis.

Influence of culture conditions on the molecular signature of mesenchymal stem cells

Cell based therapies require cells capable of self renewal and differentiation, and a prerequisite is the ability to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies is therefore an integral part of tissue engineering. Bone marrow is the most easily accessible source of mesenchymal stem cells (MSCs), and harbours two distinct populations of adult stem cells; namely hematopoietic stem cells (HSCs) and bone mesenchymal stem cells (BMSCs). Unlike HSCs, there are yet no rigorous criteria for characterizing BMSCs. Changing understanding about the pluripotency of BMSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to BMSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their in vitro study. Also, when BMSCs are cultured in vitro there is a loss of the in vivo microenvironment which results in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage number, characterized by the onset of senescence related changes. Accordingly, establishing protocols for generating large numbers of BMSCs without affecting their differentiation potential is necessary. The principal aims of this thesis were to identify potential molecular factors for characterizing BMSCs from osteoarthritic patients, and also to attempt to establish culture protocols favourable for generating large number of BMSCs, while at the same time retaining their proliferation and differentiation potential. Previously published studies concerning clonal cells have demonstrated that BMSCs are heterogeneous populations of cells at various stages of growth. Some cells are higher in the hierarchy and represent the progenitors, while other cells occupy a lower position in the hierarchy and are therefore more committed to a particular lineage. This feature of BMSCs was made evident by the work of Mareddy et al., which involved generating clonal populations of BMSCs from bone marrow of osteoarthritic patients, by a single cell clonal culture method. Proliferation potential and differentiation capabilities were used to group cells into fast growing and slow growing clones. The study presented here is a continuation of the work of Mareddy et al. and employed immunological and array based techniques to identify the primary molecular factors involved in regulating phenotypic characteristics exhibited by contrasting clonal populations. The subtractive immunization (SI) was used to generate novel antibodies against favourably expressed proteins in the fast growing clonal cell population. The difference between the clonal populations at the transcriptional level was determined using a Stem Cell RT2 Profiler TM PCR Array which focuses on stem cell pathway gene expression. Monoclonal antibodies (mAb) generated by SI were able to effectively highlight differentially expressed antigenic determinants, as was evident by Western blot analysis and confocal microscopy. Co-immunoprecipitation, followed by mass spectroscopy analysis, identified a favourably expressed protein as the cytoskeletal protein vimentin. The stem cell gene array highlighted genes that were highly upregulated in the fast growing clonal cell population. Based on their functions these genes were grouped into growth factors, cell fate determination and maintenance of embryonic and neural stem cell renewal. Furthermore, on a closer analysis it was established that the cytoskeletal protein vimentin and nine out of ten genes identified by gene array were associated with chondrogenesis or cartilage repair, consistent with the potential role played by BMSCs in defect repair and maintaining tissue homeostasis, by modulating the gene expression pattern to compensate for degenerated cartilage in osteoarthritic tissues. The gene array also presented transcripts for embryonic lineage markers such as FOXA2 and Sox2, both of which were significantly over expressed in fast growing clonal populations. A recent groundbreaking study by Yamanaka et al imparted embryonic stem cell (ESCs) -like characteristic to somatic cells in a process termed nuclear reprogramming, by the ectopic expression of the genes Sox2, cMyc and Oct4. The expression of embryonic lineage markers in adult stem cells may be a mechanism by which the favourable behaviour of fast growing clonal cells is determined and suggests a possible active phenomenon of spontaneous reprogramming in fast growing clonal cells. The expression pattern of these critical molecular markers could be indicative of the competence of BMSCs. For this reason, the expression pattern of Sox2, Oct4 and cMyc, at various passages in heterogeneous BMSCs population and tissue derived cells (osteoblasts and chondrocytes), was investigated by a real-time PCR and immunoflourescence staining. A strong nuclear staining was observed for Sox2, Oct4 and cMyc, which gradually weakened accompanied with cytoplasmic translocation after several passage. The mRNA and protein expression of Sox2, Oct4 and cMyc peaked at the third passage for osteoblasts, chondrocytes and third passage for BMSCs, and declined with each subsequent passage, indicating towards a possible mechanism of spontaneous reprogramming. This study proposes that the progressive decline in proliferation potential and multipotentiality associated with increased passaging of BMSCs in vitro might be a consequence of loss of these propluripotency factors. We therefore hypothesise that the expression of these master genes is not an intrinsic cell function, but rather an outcome of interaction of the cells with their microenvironment; this was evident by the fact that when removed from their in vivo microenvironment, BMSCs undergo a rapid loss of stemness after only a few passages. One of the most interesting aspects of this study was the integration of factors in the culture conditions, which to some extent, mimicked the in vivo microenvironmental niche of the BMSCs. A number of studies have successfully established that the cellular niche is not an inert tissue component but is of prime importance. The total sum of stimuli from the microenvironment underpins the complex interplay of regulatory mechanisms which control multiple functions in stem cells most importantly stem cell renewal. Therefore, well characterised factors which affect BMSCs characteristics, such as fibronectin (FN) coating, and morphogens such as FGF2 and BMP4, were incorporated into the cell culture conditions. The experimental set up was designed to provide insight into the expression pattern of the stem cell related transcription factors Sox2, cMyc and Oct4, in BMSCs with respect to passaging and changes in culture conditions. Induction of these pluripotency markers in somatic cells by retroviral transfection has been shown to confer pluripotency and an ESCs like state. Our study demonstrated that all treatments could transiently induce the expression of Sox2, cMyc and Oct4, and favourably affect the proliferation potential of BMSCs. The combined effect of these treatments was able to induce and retain the endogenous nuclear expression of stem cell transcription factors in BMSCs over an extended number of in vitro passages. Our results therefore suggest that the transient induction and manipulation of endogenous expression of transcription factors critical for stemness can be achieved by modulating the culture conditions; the benefit of which is to circumvent the need for genetic manipulations. In summary, this study has explored the role of BMSCs in the diseased state of osteoarthritis, by employing transcriptional profiling along with SI. In particular this study pioneered the use of primary cells for generating novel antibodies by SI. We established that somatic cells and BMSCs have a basal level of expression of pluripotency markers. Furthermore, our study indicates that intrinsic signalling mechanisms of BMSCs are intimately linked with extrinsic cues from the microenvironment and that these signals appear to be critical for retaining the expression of genes to maintain cell stemness in long term in vitro culture. This project provides a basis for developing an “artificial niche” required for reversion of commitment and maintenance of BMSC in their uncommitted homeostatic state.

Are the ‘cave’ minerals archerite (K,NH4)H2PO4 and biphosphammite (K,NH4)H2PO4 identical? A molecular structural study

The molecular structure of the mineral archerite ((K,NH4)H2PO4) has been determined and compared with that of biphosphammite ((NH4,K)H2PO4). Raman spectroscopy and infrared spectroscopy has been used to characterise these ‘cave’ minerals. Both minerals originated from the Murra-el-elevyn Cave, Eucla, Western Australia. The mineral is formed by the reaction of the chemicals in bat guano with calcite substrates. Raman and infrared bands are assigned to H2PO4-, OH and NH stretching vibrations. The Raman band at 981 cm-1 is assigned to the HOP stretching vibration. Bands in the 1200 to 1800 cm-1 region are associated with NH4+ bending modes. The molecular structure of the two minerals appear to be very similar, and it is therefore concluded that the two minerals are identical.

The sample complexity of pattern classification with neural networks: the size of the weights is more important than the size of the network

Sample complexity results from computational learning theory, when applied to neural network learning for pattern classification problems, suggest that for good generalization performance the number of training examples should grow at least linearly with the number of adjustable parameters in the network. Results in this paper show that if a large neural network is used for a pattern classification problem and the learning algorithm finds a network with small weights that has small squared error on the training patterns, then the generalization performance depends on the size of the weights rather than the number of weights. For example, consider a two-layer feedforward network of sigmoid units, in which the sum of the magnitudes of the weights associated with each unit is bounded by A and the input dimension is n. We show that the misclassification probability is no more than a certain error estimate (that is related to squared error on the training set) plus A3 √((log n)/m) (ignoring log A and log m factors), where m is the number of training patterns. This may explain the generalization performance of neural networks, particularly when the number of training examples is considerably smaller than the number of weights. It also supports heuristics (such as weight decay and early stopping) that attempt to keep the weights small during training. The proof techniques appear to be useful for the analysis of other pattern classifiers: when the input domain is a totally bounded metric space, we use the same approach to give upper bounds on misclassification probability for classifiers with decision boundaries that are far from the training examples.

Evaluating the benefits of public bicycle schemes needs to be undertaken carefully

A letter in response to an article by David Rojas-Rueda, Audrey de Nazelle, Marko Tainio, Mark J Nieuwenhuijsen, The health risks and benefits of cycling in urban environments compared with car use: health impact assessment study. BMJ 2011;343:doi:10.1136/bmj.d4521 (Published 4 August 2011) This paper sets out to compare the health benefits of the Bicing scheme (Barcelona's public bicycle share scheme) with possible risks associated with increased bicycle riding. The key variables used by the researchers include physical activity, exposure to air pollution and road traffic injury. The authors rightly identify that although traffic congestion is often a major motivator behind the establishment of public bicycle share schemes (PBSS), the health benefits may well be the largest single benefit of such schemes. Certainly PBSS appear to be one of the most effective methods of increasing the number of bicycle trips across a population, providing additional transport options and improving awareness of the possibilities bicycles offer urban transport systems. Overall, the paper is a useful addition to the literature, in that it has attempted to assess the health benefits of a large scale PBSS and weighed these against potential risks related to cyclists exposure to air pollution and road traffic injuries. Unfortunately a fundamentally flawed assumption related to the proportion of Bicing trips replacing car journeys invalidates the results of this paper. A future paper with up to date data would create a significant contribution to this emerging area within the field of sustainable transport.

The psychosocial factors influencing aggressive driving behaviour

Many drivers in highly motorised countries believe that aggressive driving is increasing. While the prevalence of the behaviour is difficult to reliably identify, the consequences of on-road aggression can be severe, with extreme cases resulting in property damage, injury and even death. This research program was undertaken to explore the nature of aggressive driving from within the framework of relevant psychological theory in order to enhance our understanding of the behaviour and to inform the development of relevant interventions. To guide the research a provisional ‘working’ definition of aggressive driving was proposed encapsulating the recurrent characteristics of the behaviour cited in the literature. The definition was: “aggressive driving is any on-road behaviour adopted by a driver that is intended to cause physical or psychological harm to another road user and is associated with feelings of frustration, anger or threat”. Two main theoretical perspectives informed the program of research. The first was Shinar’s (1998) frustration-aggression model, which identifies both the person-related and situational characteristics that contribute to aggressive driving, as well as proposing that aggressive behaviours can serve either an ‘instrumental’ or ‘hostile’ function. The second main perspective was Anderson and Bushman’s (2002) General Aggression Model. In contrast to Shinar’s model, the General Aggression Model reflects a broader perspective on human aggression that facilitates a more comprehensive examination of the emotional and cognitive aspects of aggressive behaviour. Study One (n = 48) examined aggressive driving behaviour from the perspective of young drivers as an at-risk group and involved conducting six focus groups, with eight participants in each. Qualitative analyses identified multiple situational and person-related factors that contribute to on-road aggression. Consistent with human aggression theory, examination of self-reported experiences of aggressive driving identified key psychological elements and processes that are experienced during on-road aggression. Participants cited several emotions experienced during an on-road incident: annoyance, frustration, anger, threat and excitement. Findings also suggest that off-road generated stress may transfer to the on-road environment, at times having severe consequences including crash involvement. Young drivers also appeared quick to experience negative attributions about the other driver, some having additional thoughts of taking action. Additionally, the results showed little difference between males and females in the severity of behavioural responses they were prepared to adopt, although females appeared more likely to displace their negative emotions. Following the self-reported on-road incident, evidence was also found of a post-event influence, with females being more likely to experience ongoing emotional effects after the event. This finding was evidenced by ruminating thoughts or distraction from tasks. However, the impact of such a post-event influence on later behaviours or interpersonal interactions appears to be minimal. Study Two involved the quantitative analysis of n = 926 surveys completed by a wide age range of drivers from across Queensland. The study aimed to explore the relationships between the theoretical components of aggressive driving that were identified in the literature review, and refined based on the findings of Study One. Regression analyses were used to examine participant emotional, cognitive and behavioural responses to two differing on-road scenarios whilst exploring the proposed theoretical framework. A number of socio-demographic, state and trait person-related variables such as age, pre-study emotions, trait aggression and problem-solving style were found to predict the likelihood of a negative emotional response such as frustration, anger, perceived threat, negative attributions and the likelihood of adopting either an instrumental or hostile behaviour in response to Scenarios One and Two. Complex relationships were found to exist between the variables, however, they were interpretable based on the literature review findings. Factor analysis revealed evidence supporting Shinar’s (1998) dichotomous description of on-road aggressive behaviours as being instrumental or hostile. The second stage of Study Two used logistic regression to examine the factors that predicted the potentially hostile aggressive drivers (n = 88) within the sample. These drivers were those who indicated a preparedness to engage in direct acts of interpersonal aggression on the road. Young, male drivers 17–24 years of age were more likely to be classified as potentially hostile aggressive drivers. Young drivers (17–24 years) also scored significantly higher than other drivers on all subscales of the Aggression Questionnaire (Buss & Perry, 1992) and on the ‘negative problem orientation’ and ‘impulsive careless style’ subscales of the Social Problem Solving Inventory – Revised (D’Zurilla, Nezu & Maydeu-Olivares, 2002). The potentially hostile aggressive drivers were also significantly more likely to engage in speeding and drink/drug driving behaviour. With regard to the emotional, cognitive and behavioural variables examined, the potentially hostile aggressive driver group also scored significantly higher than the ‘other driver’ group on most variables examined in the proposed theoretical framework. The variables contained in the framework of aggressive driving reliably distinguished potentially hostile aggressive drivers from other drivers (Nagalkerke R2 = .39). Study Three used a case study approach to conduct an in-depth examination of the psychosocial characteristics of n = 10 (9 males and 1 female) self-confessed hostile aggressive drivers. The self-confessed hostile aggressive drivers were aged 24–55 years of age. A large proportion of these drivers reported a Year 10 education or better and average–above average incomes. As a group, the drivers reported committing a number of speeding and unlicensed driving offences in the past three years and extensive histories of violations outside of this period. Considerable evidence was also found of exposure to a range of developmental risk factors for aggression that may have contributed to the driver’s on-road expression of aggression. These drivers scored significantly higher on the Aggression Questionnaire subscales and Social Problem Solving Inventory Revised subscales, ‘negative problem orientation’ and ‘impulsive/careless style’, than the general sample of drivers included in Study Two. The hostile aggressive driver also scored significantly higher on the Barrett Impulsivity Scale – 11 (Patton, Stanford & Barratt, 1995) measure of impulsivity than a male ‘inmate’, or female ‘general psychiatric’ comparison group. Using the Carlson Psychological Survey (Carlson, 1982), the self-confessed hostile aggressive drivers scored equal or higher scores than the comparison group of incarcerated individuals on the subscale measures of chemical abuse, thought disturbance, anti-social tendencies and self-depreciation. Using the Carlson Psychological Survey personality profiles, seven participants were profiled ‘markedly anti-social’, two were profiled ‘negative-explosive’ and one was profiled as ‘self-centred’. Qualitative analysis of the ten case study self-reports of on-road hostile aggression revealed a similar range of on-road situational factors to those identified in the literature review and Study One. Six of the case studies reported off-road generated stress that they believed contributed to the episodes of aggressive driving they recalled. Intense ‘anger’ or ‘rage’ were most frequently used to describe the emotions experienced in response to the perceived provocation. Less frequently ‘excitement’ and ‘fear’ were cited as relevant emotions. Notably, five of the case studies experienced difficulty articulating their emotions, suggesting emotional difficulties. Consistent with Study Two, these drivers reported negative attributions and most had thoughts of aggressive actions they would like to take. Similarly, these drivers adopted both instrumental and hostile aggressive behaviours during the self-reported incident. Nine participants showed little or no remorse for their behaviour and these drivers also appeared to exhibit low levels of personal insight. Interestingly, few incidents were brought to the attention of the authorities. Further, examination of the person-related characteristics of these drivers indicated that they may be more likely to have come from difficult or dysfunctional backgrounds and to have a history of anti-social behaviours on and off the road. The research program has several key theoretical implications. While many of the findings supported Shinar’s (1998) frustration-aggression model, two key areas of difference emerged. Firstly, aggressive driving behaviour does not always appear to be frustration driven, but can also be driven by feelings of excitation (consistent with the tenets of the General Aggression Model). Secondly, while the findings supported a distinction being made between instrumental and hostile aggressive behaviours, the characteristics of these two types of behaviours require more examination. For example, Shinar (1998) proposes that a driver will adopt an instrumental aggressive behaviour when their progress is impeded if it allows them to achieve their immediate goals (e.g. reaching their destination as quickly as possible); whereas they will engage in hostile aggressive behaviour if their path to their goal is blocked. However, the current results question this assertion, since many of the hostile aggressive drivers studied appeared prepared to engage in hostile acts irrespective of whether their goal was blocked or not. In fact, their behaviour appeared to be characterised by a preparedness to abandon their immediate goals (even if for a short period of time) in order to express their aggression. The use of the General Aggression Model enabled an examination of the three components of the ‘present internal state’ comprising emotions, cognitions and arousal and how these influence the likelihood of a person responding aggressively to an on-road situation. This provided a detailed insight into both the cognitive and emotional aspects of aggressive driving that have important implications for the design of relevant countermeasures. For example, the findings highlighted the potential value of utilising Cognitive Behavioural Therapy with aggressive drivers, particularly the more hostile offenders. Similarly, educational efforts need to be mindful of the way that person-related factors appear to influence one’s perception of another driver’s behaviour as aggressive or benign. Those drivers with a predisposition for aggression were more likely to perceive aggression or ‘wrong doing’ in an ambiguous on-road situation and respond with instrumental and/or hostile behaviour, highlighting the importance of perceptual processes in aggressive driving behaviour.

Common variation in the fibroblast growth factor receptor 2 gene is not associated with endometriosis risk

BACKGROUND Endometriosis is a polygenic disease with a complex and multifactorial aetiology that affects 8-10% of women of reproductive age. Epidemiological data support a link between endometriosis and cancers of the reproductive tract. Fibroblast growth factor receptor 2 (FGFR2) has recently been implicated in both endometrial and breast cancer. Our previous studies on endometriosis identified significant linkage to a novel susceptibility locus on chromosome 10q26 and the FGFR2 gene maps within this linkage region. We therefore hypothesized that variation in FGFR2 may contribute to the risk of endometriosis. METHODS We genotyped 13 single nucleotide polymorphisms (SNPs) densely covering a 27 kb region within intron 2 of FGFR2 including two SNPs (rs2981582 and rs1219648) significantly associated with breast cancer and a total 40 tagSNPs across 150 kb of the FGFR2 gene. SNPs were genotyped in 958 endometriosis cases and 959 unrelated controls. RESULTS We found no evidence for association between endometriosis and FGFR2 intron 2 SNPs or SNP haplotypes and no evidence for association between endometriosis and variation across the FGFR2 gene. CONCLUSIONS Common variation in the breast-cancer implicated intron 2 and other highly plausible causative candidate regions of FGFR2 do not appear to be a major contributor to endometriosis susceptibility in our large Australian sample.

A forced titration study of the antioxidant and immunomodulatory effects of Ambrotose AO supplement

Background Oxidative stress plays a role in acute and chronic inflammatory disease and antioxidant supplementation has demonstrated beneficial effects in the treatment of these conditions. This study was designed to determine the optimal dose of an antioxidant supplement in healthy volunteers to inform a Phase 3 clinical trial. Methods The study was designed as a combined Phase 1 and 2 open label, forced titration dose response study in healthy volunteers (n = 21) to determine both acute safety and efficacy. Participants received a dietary supplement in a forced titration over five weeks commencing with a no treatment baseline through 1, 2, 4 and 8 capsules. The primary outcome measurement was ex vivo changes in serum oxygen radical absorbance capacity (ORAC). The secondary outcome measures were undertaken as an exploratory investigation of immune function. Results A significant increase in antioxidant activity (serum ORAC) was observed between baseline (no capsules) and the highest dose of 8 capsules per day (p = 0.040) representing a change of 36.6%. A quadratic function for dose levels was fitted in order to estimate a dose response curve for estimating the optimal dose. The quadratic component of the curve was significant (p = 0.047), with predicted serum ORAC scores increasing from the zero dose to a maximum at a predicted dose of 4.7 capsules per day and decreasing for higher doses. Among the secondary outcome measures, a significant dose effect was observed on phagocytosis of granulocytes, and a significant increase was also observed on Cox 2 expression. Conclusion This study suggests that Ambrotose AO® capsules appear to be safe and most effective at a dosage of 4 capsules/day. It is important that this study is not over interpreted; it aimed to find an optimal dose to assess the dietary supplement using a more rigorous clinical trial design. The study achieved this aim and demonstrated that the dietary supplement has the potential to increase antioxidant activity. The most significant limitation of this study was that it was open label Phase 1/Phase 2 trial and is subject to potential bias that is reduced with the use of randomization and blinding. To confirm the benefits of this dietary supplement these effects now need to be demonstrated in a Phase 3 randomised controlled trial (RCT).

Morphological classification of bovine ovarian follicles

Follicle classification is an important aid to the understanding of follicular development and atresia. Some bovine primordial follicles have the classical primordial shape, but ellipsoidal shaped follicles with some cuboidal granulosa cells at the poles are far more common. Preantral follicles have one of two basal lamina phenotypes, either a single aligned layer or one with additional layers. In antral follicles <5 mm diameter, half of the healthy follicles have columnar shaped basal granulosa cells and additional layers of basal lamina, which appear as loops in cross section (‘loopy’). The remainder have aligned single-layered follicular basal laminas with rounded basal cells, and contain better quality oocytes than the loopy/columnar follicles. In sizes >5 mm, only aligned/rounded phenotypes are present. Dominant and subordinate follicles can be identified by ultrasound and/or histological examination of pairs of ovaries. Atretic follicles <5 mm are either basal atretic or antral atretic, named on the basis of the location in the membrana granulosa where cells die first. Basal atretic follicles have considerable biological differences to antral atretic follicles. In follicles >5 mm, only antral atresia is observed. The concentrations of follicular fluid steroid hormones can be used to classify atresia and distinguish some of the different types of atresia; however, this method is unlikely to identify follicles early in atresia, and hence misclassify them as healthy. Other biochemical and histological methods can be used, but since cell death is a part of normal homoeostatis, deciding when a follicle has entered atresia remains somewhat subjective.

Identifying optimal lipid raft characteristics required to promote nanoscale protein-protein interactions on the plasma membrane

The dynamic lateral segregation of signaling proteins into microdomains is proposed to facilitate signal transduction, but the constraints on microdomain size, mobility, and diffusion that might realize this function are undefined. Here we interrogate a stochastic spatial model of the plasma membrane to determine how microdomains affect protein dynamics. Taking lipid rafts as representative microdomains, we show that reduced protein mobility in rafts segregates dynamically partitioning proteins, but the equilibrium concentration is largely independent of raft size and mobility. Rafts weakly impede small-scale protein diffusion but more strongly impede long-range protein mobility. The long-range mobility of raft-partitioning and raft-excluded proteins, however, is reduced to a similar extent. Dynamic partitioning into rafts increases specific interprotein collision rates, but to maximize this critical, biologically relevant function, rafts must be small (diameter, 6 to 14 nm) and mobile. Intermolecular collisions can also be favored by the selective capture and exclusion of proteins by rafts, although this mechanism is generally less efficient than simple dynamic partitioning. Generalizing these results, we conclude that microdomains can readily operate as protein concentrators or isolators but there appear to be significant constraints on size and mobility if microdomains are also required to function as reaction chambers that facilitate nanoscale protein-protein interactions. These results may have significant implications for the many signaling cascades that are scaffolded or assembled in plasma membrane microdomains.

Applications for advice from courts by insolvency practitioners

This article examines the nature of the powers of insolvency practitioners in applying for advice from the courts. It examines first the policy justification for granting these unusual rights to insolvency practitioners having regard to the nature of the work undertaken in the modern insolvency context. Second, the notion that subtle differences exist in relation to seeking advice from the courts in different types of administrations is explored. The question then as to whether it is appropriate that such differences exist, given that the policy basis of an insolvency practitioner seeking advice in different administrations does not appear to be different, is considered. Conclusions are drawn in favour of a consistent approach across all types of administration and suggestions are made for the legislation to be altered to provide a single set of provisions around this issue.