Motor controller simulation and embedded implementation for a blood pump

This study was a step forward in modeling, simulation and microcontroller implementation of a high performance control algorithm for the motor of a blood pump. The rotor angle is sensed using three Hall effect sensors and an algorithm is developed to obtain better angular resolution from the three signals for better discrete-time updates of the controller. The performance of the system was evaluated in terms of actual and reference speeds, stator currents and power consumption over a range of reference speeds up to 4000 revolutions per minute. The use of fewer low cost Hall effect sensors compared to expensive high resolution sensors could reduce the cost of blood pumps for total artificial hearts.

Characterization of ENU-induced mutations in red blood cell structural proteins

Murine models with modified gene function as a result of N-ethyl-N-nitrosourea (ENU) mutagenesis have been used to study phenotypes resulting from genetic change. This study investigated genetic factors associated with red blood cell (RBC) physiology and structural integrity that may impact on blood component storage and transfusion outcome. Forward and reverse genetic approaches were employed with pedigrees of ENU-treated mice using a homozygous recessive breeding strategy. In a “forward genetic” approach, pedigree selection was based upon identification of an altered phenotype followed by exome sequencing to identify a causative mutation. In a second strategy, a “reverse genetic” approach based on selection of pedigrees with mutations in genes of interest was utilised and, following breeding to homozygosity, phenotype assessed. Thirty-three pedigrees were screened by the forward genetic approach. One pedigree demonstrated reticulocytosis, microcytic anaemia and thrombocytosis. Exome sequencing revealed a novel single nucleotide variation (SNV) in Ank1 encoding the RBC structural protein ankyrin-1 and the pedigree was designated Ank1EX34. The reticulocytosis and microcytic anaemia observed in the Ank1EX34 pedigree were similar to clinical features of hereditary spherocytosis in humans. For the reverse genetic approach three pedigrees with different point mutations in Spnb1 encoding RBC protein spectrin-1β, and one pedigree with a mutation in Epb4.1, encoding band 4.1 were selected for study. When bred to homozygosity two of the spectrin-1β pedigrees (a, b) demonstrated increased RBC count, haemoglobin (Hb) and haematocrit (HCT). The third Spnb1 mutation (spectrin-1β c) and mutation in Epb4.1 (band 4.1) did not significantly affect the haematological phenotype, despite these two mutations having a PolyPhen score predicting the mutation may be damaging. Exome sequencing allows rapid identification of causative mutations and development of databases of mutations predicted to be disruptive. These tools require further refinement but provide new approaches to the study of genetically defined changes that may impact on blood component storage and transfusion outcome.

Revascularization and tissue regeneration of an empty root canal space is enhanced by a direct blood supply and stem cells

Background Regenerative endodontics is an innovative treatment concept aiming to regenerate pulp, dentin and root structures. In the diseased or necrotic tooth, the limitation in vascular supply renders successful tissue regeneration/generation in a whole tooth challenging. The aim of this study is to evaluate the ability of vascularized tissue to develop within a pulpless tooth using tissue engineering techniques. Materials and methods A pulpless tooth chamber, filled with collagen I gel containing isolated rat dental pulp cells (DPC) and angiogenic growth factors, was placed into a hole created in the femoral cortex or into its own tooth socket, respectively. The gross, histological and biochemical characteristics of the de novo tissue were evaluated at 4 and 8weeks post-transplantation. Results Tooth revascularization and tissue generation was observed only in the femur group, confirming the important role of vascular supply in tissue regeneration. The addition of cells and growth factors significantly promoted connective tissue production in the tooth chamber. Conclusion Successful revascularization and tissue regeneration in this model demonstrate the importance of a direct vascular supply and the advantages of a stem cell approach. © 2012 John Wiley & Sons A/S.

Self-regulation from birth to age seven : associations with maternal mental health, parenting, and social, emotional and behavioural outcomes for children

Self-regulation refers to our individual capacities to regulate our behaviours, emotions, and thoughts, with these skills developing rapidly across early childhood. This thesis examined sleep, emotional, and cognitive regulation development, and related parental influences, for children participating in the Longitudinal Study of Australian Children. Important longitudinal associations among children's self-regulation, maternal mental health, parenting, and later behaviour problems for children were also investigated. A unique contribution of this research was a prevalence estimate of early childhood self-regulation problems in Australian children that was documented for the first time.

Formation of blood clot on biomaterial implants influences bone healing

The first step in bone healing is forming a blood clot at injured bones. During bone implantation, biomaterials unavoidably come into direct contact with blood, leading to a blood clot formation on its surface prior to bone regeneration. Despite both situations being similar in forming a blood clot at the defect site, most research in bone tissue engineering virtually ignores the important role of a blood clot in supporting healing. Dental implantology has long demonstrated that the fibrin structure and cellular content of a peri-implant clot can greatly affect osteoconduction and de novo bone formation on implant surfaces. This paper reviews the formation of a blood clot during bone healing in related to the use of platelet-rich plasma (PRP) gels. It is implicated that PRP gels are dramatically altered from a normal clot in healing, resulting conflicting effect on bone regeneration. These results indicate that the effect of clots on bone regeneration depends on how the clots are formed. Factors that influence blood clot structure and properties in related to bone healing are also highlighted. Such knowledge is essential for developing strategies to optimally control blood clot formation, which ultimately alter the healing microenvironment of bone. Of particular interest are modification of surface chemistry of biomaterials, which displays functional groups at varied composition for the purpose of tailoring blood coagulation activation, resultant clot fibrin architecture, rigidity, susceptibility to lysis, and growth factor release. This opens new scope of in situ blood clot modification as a promising approach in accelerating and controlling bone regeneration.

Reversible transdifferentiation of blood vascular endothelial cells to a lymphatic-like phenotype in vitro

Blood vascular cells and lymphatic endothelial cells (BECs and LECs, respectively) form two separate vascular systems and are functionally distinct cell types or lineages with characteristic gene expression profiles. Interconversion between these cell types has not been reported. Here, we show that in conventional in vitro angiogenesis assays, human BECs of fetal or adult origin show altered gene expression that is indicative of transition to a lymphatic-like phenotype. This change occurs in BECs undergoing tubulogenesis in fibrin, collagen or Matrigel assays, but is independent of tube formation per se, because it is not inhibited by a metalloproteinase inhibitor that blocks tubulogenesis. It is also reversible, since cells removed from 3D tubules revert to a BEC expression profile upon monolayer culture. Induction of the lymphatic-like phenotype is partially inhibited by co-culture of HUVECs with perivascular cells. These data reveal an unexpected plasticity in endothelial phenotype, which is regulated by contact with the ECM environment and/or cues from supporting cells.

Time course analysis of hypoxia, granulation tissue and blood vessel growth, and remodeling in healing rat cutaneous incisional primary intention wounds

Hypoxia and the development and remodeling of blood vessels and connective tissue in granulation tissue that forms in a wound gap following full-thickness skin incision in the rat were examined as a function of time. A 1.5 cm-long incisional wound was created in rat groin skin and the opposed edges sutured together. Wounds were harvested between 3 days and 16 weeks and hypoxia, percent vascular volume, cell proliferation and apoptosis, α-smooth muscle actin, vascular endothelial growth factor-A, vascular endothelial growth factor receptor-2, and transforming growth factor-β 1 expression in granulation tissue were then assessed. Hypoxia was evident between 3 and 7 days while maximal cell proliferation at 3 days (123.6 ± 22.2 cells/mm 2, p < 0.001 when compared with normal skin) preceded the peak percent vascular volume that occurred at 7 days (15.83 ± 1.10%, p < 0.001 when compared with normal skin). The peak in cell apoptosis occurred at 3 weeks (12.1 ± 1.3 cells/mm 2, p < 0.001 when compared with normal skin). Intense α-smooth muscle actin labeling in myofibroblasts was evident at 7 and 10 days. Vascular endothelial growth factor receptor-2 and vascular endothelial growth factor-A were detectable until 2 and 3 weeks, respectively, while transforming growth factor-β 1 protein was detectable in endothelial cells and myofibroblasts until 3-4 weeks and in the extracellular matrix for 16 weeks. Incisional wound granulation tissue largely developed within 3-7 days in the presence of hypoxia. Remodeling, marked by a decline in the percent vascular volume and increased cellular apoptosis, occurred largely in the absence of detectable hypoxia. The expression of vascular endothelial growth factor-A, vascular endothelial growth factor receptor-2, and transforming growth factor-β 1 is evident prior, during, and after the peak of vascular volume reflecting multiple roles for these factors during wound healing.

Investigating online recognition for blood donor retention : an experiential donor value approach

Recognising that charitable behaviour can be motivated by public recognition and emotional satisfaction, not-for-profit organisations have developed strategies that leverage self-interest over altruism by facilitating individuals to donate conspicuously. Initially developed as novel marketing programs to increase donation income, such conspicuous tokens of recognition are being recognised as important value propositions to nurture donor relationships. Despite this, there is little empirical evidence that identifies when donations can be increased through conspicuous recognition. Furthermore, social media’s growing popularity for self-expression, as well as the increasing use of technology in donor relationship management strategies, makes an examination of virtual conspicuous tokens of recognition in relation to what value donors seek particularly insightful. Therefore, this research examined the impact of experiential donor value and virtual conspicuous tokens of recognition on blood donor intentions. Using online survey data from 186 Australian blood donors, results show that in fact emotional value is a stronger predictor of intentions to donate blood than altruistic value, while social value is the strongest predictor of intentions if provided with recognition. Clear linkages between dimensions of donor value (altruistic, emotional and social) and conspicuous donation behaviour (CDB) were identified. The findings provide valuable insights into the use of conspicuous donation tokens of recognition on social media, and contribute to our understanding into the under-researched areas of donor value and CDB.

Maternal feeding self-efficacy and fruit and vegetable intakes in infants. Results from the SAIDI study

Adequate consumption of fruits and vegetables (FV) is a characteristic of a healthy diet but remains a challenge in nutrition interventions. This cross-sectional study explored the multi-directional relationships between maternal feeding self-efficacy, parenting confidence, child feeding behaviour, exposure to new food and FV intake in a cohort of 277 infants. Mothers with healthy infants weighing ≥2500 g and ≥37 weeks gestation were recruited post-natally from 11 South Australian hospitals. Socio-demographic datawere collected at recruitment. At 6 months postnatal, infantswereweighed and measured, andmothers completed a questionnaire exploring their perceptions of child feeding behaviour and child exposure to newfoods. The questionnaire also included the Short Temperament Scale for Infants, Kessler 10 to measure maternal psychological distress and 5 items measuring maternal feeding self-efficacy. The number of occasions and variety of FV (number of subgroups within food groups) consumed by infants were estimated from a 24-hour dietary recall and 2 days food record. Structural equation modellingwas performed using Mplus version 6.11. Median (IQR) variety scores were 2 (1–3) for fruit and 3 (2–5) for vegetable intake. The most popular FV consumed were apple (n = 108, 45.0%) and pumpkin (n = 143, 56.3%). None of the variables studied predicted the variety of child fruit intake. Parenting confidence, exposure to new foods and child feeding behaviourwere indirectly related to child vegetable intake through maternal feeding self-efficacy while total number of children negatively predicted child vegetable variety (p < 0.05). This highlights the need for addressing antecedents of maternal feeding self-efficacy and the family eating environment as key strategies towards development of healthy eating in children.

Improving the detection of donations within the RHD negative blood donor panel which weakly express the RHD antigen

This project improved the detection and classification of very weakly expressed RhD variants in the Australian blood donor panel and contributed to the knowledge of anti-D reactivity patterns of RHD alleles that are undescribed. As such, the management of donations possessing these RHD alleles can be improved upon and the overall safety of transfusion medicine pertaining to the Rh blood group system will be increased. Future projects at ARCBS will be able to utilise the procedures developed in this project, thereby decreasing throughput time. The specificity of current testing will be improved and the need for outsourced RHD testing diminished.

The influence of maternal infant feeding practices and beliefs on the expression of food neophobia in toddlers

Food neophobia is a highly heritable trait characterized by the rejection of foods that are novel or unknown and potentially limits dietary variety, with lower intake and preference particularly for fruits and vegetables. Understanding non-genetic (environmental) factors that may influence the expression of food neophobia is essential to improving children’s consumption of fruits and vegetables and encouraging the adoption of healthier diets. The aim of this study was to examine whether maternal infant feeding beliefs (at four months) were associated with the expression of food neophobia in toddlers and whether controlling feeding practices mediated this relationship. Participants were 244 first-time mothers (M = 30.4, SD = 5.1 years) allocated to the control group of the NOURISH randomized controlled trial. The relationships between infant feeding beliefs (Infant Feeding Questionnaire) at four months and controlling child feeding practices (Child Feeding Questionnaire) and food neophobia (Child Food Neophobia Scale) at 24 months were tested using correlational and multiple linear regression models (adjusted for significant covariates). Higher maternal Concern about infant under-eating and becoming underweight at four months was associated with higher child food neophobia at two years. Similarly, lower Awareness of infant hunger and satiety cues was associated with higher child food neophobia. Both associations were significantly mediated by mothers’ use of Pressure to eat. Intervening early to promote positive feeding practices to mothers may help reduce the use of controlling practices as children develop. Further research that can further elucidate the bi-directional nature of the mother-child feeding relationship is still required.

Critical dependence of blood-borne biomarker concentrations on the half-lives of their carrier proteins

Until recently, the low-abundance (LA) range of the serum proteome was an unexplored reservoir of diagnostic information. Today it is increasingly appreciated that a diagnostic goldmine of LA biomarkers resides in the blood stream in complexed association with more abundant higher molecular weight carrier proteins such as albumin and immunoglobulins. As we now look to the possibility of harvesting these LA biomarkers more efficiently through engineered nano-scale particles, mathematical approaches are needed in order to reveal the mechanisms by which blood carrier proteins act as molecular 'mops' for LA diagnostic cargo, and the functional relationships between bound LA biomarker concentrations and other variables of interest such as biomarker intravasation and clearance rates and protein half-lives in the bloodstream. Here we show, by simple mathematical modeling, how the relative abundance of large carrier proteins and their longer half-lives in the bloodstream work together to amplify the total blood concentration of these tiny biomarkers. The analysis further suggests that alterations in the production of biomarkers lead to gradual rather than immediate changes in biomarker levels in the blood circulation. The model analysis also points to the characteristics of artificial nano-particles that would render them more efficient harvesters of tumor biomarkers in the circulation, opening up possibilities for the early detection of curable disease, rather than simply better detection of advanced disease.

Beliefs about infant regulation, early infant behaviors and maternal postnatal depressive symptoms

Background: Young infants may have irregular sleeping and feeding patterns. Such regulation difficulties are known correlates of maternal depressive symptoms. Parental beliefs regarding their role in regulating infant behaviours also may play a role. We investigated the association of depressive symptoms with infant feeding/sleeping behaviours, parent regulation beliefs, and the interaction of the two. Method: In 2006, 272 mothers of infants aged up to 24 weeks completed a questionnaire about infant behaviour and regulation beliefs. Participants were recruited from general medical practices and child health clinics in Brisbane, Australia. Depressive symptomology was measured using the Edinburgh Postnatal Depression Scale (EPDS). Other measures were adapted from the ALSPAC study. Results: Regression analyses were run controlling for partner support, other support, life events, and a range of demographic variables. Maternal depressive symptoms were associated with infant sleeping and feeding problems but not regulation beliefs. The most important infant predictor was sleep behaviours with feeding behaviours accounting for little additional variance. An interaction between regulation beliefs and sleep behaviours was found. Mothers with high regulation beliefs were more susceptible to postnatal depressive symptoms when infant sleep behaviours were problematic. Conclusion: Mothers of young infants who expect greater control are more susceptible to depressive symptoms when their infant presents challenging sleep behaviour.

Blood transfer devices for malaria rapid diagnostic tests : evaluation of accuracy, safety and ease of use

Background: Malaria rapid diagnostic tests (RDTs) are increasingly used by remote health personnel with minimal training in laboratory techniques. RDTs must, therefore, be as simple, safe and reliable as possible. Transfer of blood from the patient to the RDT is critical to safety and accuracy, and poses a significant challenge to many users. Blood transfer devices were evaluated for accuracy and precision of volume transferred, safety and ease of use, to identify the most appropriate devices for use with RDTs in routine clinical care. Methods: Five devices, a loop, straw-pipette, calibrated pipette, glass capillary tube, and a new inverted cup device, were evaluated in Nigeria, the Philippines and Uganda. The 227 participating health workers used each device to transfer blood from a simulated finger-prick site to filter paper. For each transfer, the number of attempts required to collect and deposit blood and any spilling of blood during transfer were recorded. Perceptions of ease of use and safety of each device were recorded for each participant. Blood volume transferred was calculated from the area of blood spots deposited on filter paper. Results: The overall mean volumes transferred by devices differed significantly from the target volume of 5 microliters (p < 0.001). The inverted cup (4.6 microliters) most closely approximated the target volume. The glass capillary was excluded from volume analysis as the estimation method used is not compatible with this device. The calibrated pipette accounted for the largest proportion of blood exposures (23/225, 10%); exposures ranged from 2% to 6% for the other four devices. The inverted cup was considered easiest to use in blood collection (206/ 226, 91%); the straw-pipette and calibrated pipette were rated lowest (143/225 [64%] and 135/225 [60%] respectively). Overall, the inverted cup was the most preferred device (72%, 163/227), followed by the loop (61%, 138/227). Conclusions: The performance of blood transfer devices varied in this evaluation of accuracy, blood safety, ease of use, and user preference. The inverted cup design achieved the highest overall performance, while the loop also performed well. These findings have relevance for any point-of-care diagnostics that require blood sampling.

Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet

Glucocorticoid hormones are critical to respond and adapt to stress. Genetic variations in the glucocorticoid receptor (GR) gene alter hypothalamic-pituitary-adrenal (HPA) axis activity and associate with hypertension and susceptibility to metabolic disease. Here we test the hypothesis that reduced GR density alters blood pressure and glucose and lipid homeostasis and limits adaption to obesogenic diet. Heterozygous GR βgeo/+ mice were generated from embryonic stem (ES) cells with a gene trap integration of a β-galactosidase-neomycin phosphotransferase (βgeo) cassette into the GR gene creating a transcriptionally inactive GR fusion protein. Although GRβgeo/+ mice have 50% less functional GR, they have normal lipid and glucose homeostasis due to compensatory HPA axis activation but are hypertensive due to activation of the renin-angiotensin- aldosterone system (RAAS). When challenged with a high-fat diet, weight gain, adiposity, and glucose intolerance were similarly increased in control and GRβgeo/+ mice, suggesting preserved control of intermediary metabolism and energy balance. However, whereas a high-fat diet caused HPA activation and increased blood pressure in control mice, these adaptions were attenuated or abolished in GRβgeo/+ mice. Thus, reduced GR density balanced by HPA activation leaves glucocorticoid functions unaffected but mineralocorticoid functions increased, causing hypertension. Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet.