Circulating fragments of N-Terminal Pro-B-Type Natriuretic Peptides in plasma of heart failure patients

BACKGROUND: The use of nonstandardized N-terminal pro-B-type natriuretic peptide (NT-proBNP) assays can contribute to the misdiagnosis of heart failure (HF). Moreover, there is yet to be established a common consensus regarding the circulating forms of NT-proBNP being used in current assays. We aimed to characterize and quantify the various forms of NT-proBNP in the circulation of HF patients. METHODS: Plasma samples were collected from HF patients (n = 20) at rest and stored at -80 degrees C. NT-proBNP was enriched from HF patient plasma by use of immunoprecipitation followed by mass spectrometric analysis. Customized homogeneous sandwich AlphaLISA (R) immunoassays were developed and validated to quantify 6 fragments of NT-proBNP. RESULTS: Mass spectrometry identified the presence of several N- and C-terminally processed forms of circulating NT-proBNP, with physiological proteolysis between Pro2-Leu3, Leu3-Gly4, Pro6-Gly7, and Pro75-Arg76. Consistent with this result, AlphaLISA immunoassays demonstrated that antibodies targeting the extreme N or C termini measured a low apparent concentration of circulating NT-proBNP. The apparent circulating NT-proBNP concentration was increased with antibodies targeting nonglycosylated and nonterminal epitopes (P < 0.05). CONCLUSIONS: In plasma collected from HF patients, immunoreactive NT-proBNP was present as multiple N- and C-terminally truncated fragments of the full length NT-proBNP molecule. Immunodetection of NT-proBNP was significantly improved with the use of antibodies that did not target these terminal regions. These findings support the development of a next generation NT-proBNP assay targeting nonterminal epitopes as well as avoiding the central glycosylated region of this molecule. (c) 2013 American Association for Clinical Chemistry

A rapid and cost-effective method of producing recombinant proBNP and NT-proBNP variants in Escherichia coli for immunoassay of heart failure

The measurements of plasma natriuretic peptides (NT-proBNP, proBNP and BNP) are used to diagnose heart failure but these are expensive to produce. We describe a rapid, cheap and facile production of proteins for immunoassays of heart failure. DNA encoding N-terminally His-tagged NT-proBNP and proBNP were cloned into the pJexpress404 vector. ProBNP and NT-proBNP peptides were expressed in Escherichia coli, purified and refolded in vitro. The analytical performance of these peptides were comparable with commercial analytes (NT-proBNP EC50 for the recombinant is 2.6 ng/ml and for the commercial material is 5.3 ng/ml) and the EC50 for recombinant and commercial proBNP, are 3.6 and 5.7 ng/ml respectively). Total yield of purified refolded NT-proBNP peptide was 1.75 mg/l and proBNP was 0.088 mg/l. This approach may also be useful in expressing other protein analytes for immunoassay applications. To develop a cost effective protein expression method in E. coli to obtain high yields of NT-proBNP (1.75 mg/l) and proBNP (0.088 mg/l) peptides for immunoassay use.

Can measures of limb loading and dynamic stability during the squat maneuver provide an index of early functional recovery following unilateral total hip arthroplasty?

Objective: To investigate limb loading and dynamic stability during squatting in the early functional recovery of total hip arthroplasty (THA) patients. Design: Cohort study Setting: Inpatient rehabilitation clinic. Participants: A random sample of 61 THA patients (34♂/27♀; 62±9 yrs, 77±14 kg, 174±9 cm) was assessed twice, 13.2±3.8 days (PRE) and 26.6±3.3 days post-surgery (POST), and compared with a healthy reference group (REF) (22♂/16♀; 47±12yrs; 78±20kg; 175±10cm). Interventions: THA patients received two weeks of standard in-patient rehabilitation. Main Outcome Measure(s): Inter-limb vertical force distribution and dynamic stability during the squat maneuver, as defined by the root mean square (RMS) of the center of pressure in antero-posterior and medio-lateral directions, of operated (OP) and non-operated (NON)limbs. Self-reported function was assessed via FFb-H-OA 2.0 questionnaire. Results: At PRE, unloading of the OP limb was 15.8% greater (P<.001, d=1.070) and antero-posterior and medio-lateral center of pressure RMS were 30-34% higher in THA than REF P<.05). Unloading was reduced by 12.8% towards a more equal distribution from PRE to POST (P<.001, d=0.874). Although medio-lateral stability improved between PRE and POST (OP: 14.8%, P=.024, d=0.397; NON: 13.1%, P=.015, d=0.321), antero-posterior stability was not significantly different. Self-reported physical function improved by 15.8% (P<.001, d=0.965). Conclusion(s): THA patients unload the OP limb and are dynamically more unstable during squatting in the early rehabilitation phase following total hip replacement than healthy adults. Although loading symmetry and medio-lateral stability improved to the level of healthy adults with rehabilitation, antero-posterior stability remained impaired. Measures of dynamic stability and load symmetry during squatting provide quantitative information that can be used to clinically monitor early functional recovery from THA.

Resilience of water supply systems in meeting the challenges posed by climate change and population growth

This research project provides a scientifically robust approach for assessing the resilience of water supply systems, which are critical infrastructure, to impacts of climate change and population growth. An approach for the identification of trigger points that allows timely and appropriate management actions to be taken to avoid catastrophic system failure is an important outcome of this project. In the current absence of a formal method to evaluate the resilience of a water supply system, the approach developed in this study was based on the characterisation of resilience of a water supply system to a range of surrogate measures. Accordingly, a set of indicators are proposed to evaluate system behaviour and logistic regression analysis was used to assess system behaviour under predicted rainfall, storage and demand conditions.

The N170 observed ‘in the wild’: robust event-related potentials to faces in cluttered dynamic visual scenes

As a social species in a constantly changing environment, humans rely heavily on the informational richness and communicative capacity of the face. Thus, understanding how the brain processes information about faces in real-time is of paramount importance. The N170 is a high temporal resolution electrophysiological index of the brain's early response to visual stimuli that is reliably elicited in carefully controlled laboratory-based studies. Although the N170 has often been reported to be of greatest amplitude to faces, there has been debate regarding whether this effect might be an artifact of certain aspects of the controlled experimental stimulation schedules and materials. To investigate whether the N170 can be identified in more realistic conditions with highly variable and cluttered visual images and accompanying auditory stimuli we recorded EEG 'in the wild', while participants watched pop videos. Scene-cuts to faces generated a clear N170 response, and this was larger than the N170 to transitions where the videos cut to non-face stimuli. Within participants, wild-type face N170 amplitudes were moderately correlated to those observed in a typical laboratory experiment. Thus, we demonstrate that the face N170 is a robust and ecologically valid phenomenon and not an artifact arising as an unintended consequence of some property of the more typical laboratory paradigm.

Symptom correlates of static and dynamic facial affect processing in schizophrenia : evidence of a double dissociation?

Schizophrenia patients have been shown to be compromised in their ability to recognize facial emotion. This deficit has been shown to be related to negative symptoms severity. However, to date, most studies have used static rather than dynamic depictions of faces. Nineteen patients with schizophrenia were compared with seventeen controls on 2 tasks; the first involving the discrimination of facial identity, emotion, and butterfly wings; the second testing emotion recognition using both static and dynamic stimuli. In the first task, the patients performed more poorly than controls for emotion discrimination only, confirming a specific deficit in facial emotion recognition. In the second task, patients performed more poorly in both static and dynamic facial emotion processing. An interesting pattern of associations suggestive of a possible double dissociation emerged in relation to correlations with symptom ratings: high negative symptom ratings were associated with poorer recognition of static displays of emotion, whereas high positive symptom ratings were associated with poorer recognition of dynamic displays of emotion. However, while the strength of associations between negative symptom ratings and accuracy during static and dynamic facial emotion processing was significantly different, those between positive symptom ratings and task performance were not. The results confirm a facial emotion-processing deficit in schizophrenia using more ecologically valid dynamic expressions of emotion. The pattern of findings may reflect differential patterns of cortical dysfunction associated with negative and positive symptoms of schizophrenia in the context of differential neural mechanisms for the processing of static and dynamic displays of facial emotion.

Numerical studies on CFRP strengthened steel columns under transverse impact

Strengthening of metallic structures using carbon fibre reinforced polymer (CFRP) has become a smart strengthening option over the conventional strengthening method. Transverse impact loading due to accidental vehicular collision can lead to the failure of existing steel hollow tubular columns. However, knowledge is very limited on the behaviour of CFRP strengthened steel members under dynamic impact loading condition. This paper deals with the numerical simulation of CFRP strengthened square hollow section (SHS) steel columns under transverse impact loading to predict the behaviour and failure modes. The transverse impact loading is simulated using finite element (FE) analysis based on numerical approach. The accuracy of the FE modelling is ensured by comparing the predicted results with available experimental tests. The effects of impact velocity, impact mass, support condition, axial loading and CFRP thickness are examined through detail parametric study. The impact simulation results indicate that the strengthening technique shows an improved impact resistance capacity by reducing lateral displacement of the strengthened column about 58% compared to the bare steel column. Axial loading plays an important role on the failure behaviour of tubular column.

Steady state visually evoked potential correlates of static and dynamic emotional face processing

While the neural regions associated with facial identity recognition are considered to be well defined, the neural correlates of non-moving and moving images of facial emotion processing are less clear. This study examined the brain electrical activity changes in 26 participants (14 males M = 21.64, SD = 3.99; 12 females M = 24.42, SD = 4.36), during a passive face viewing task, a scrambled face task and separate emotion and gender face discrimination tasks. The steady state visual evoked potential (SSVEP) was recorded from 64-electrode sites. Consistent with previous research, face related activity was evidenced at scalp regions over the parieto-temporal region approximately 170 ms after stimulus presentation. Results also identified different SSVEP spatio-temporal changes associated with the processing of static and dynamic facial emotions with respect to gender, with static stimuli predominately associated with an increase in inhibitory processing within the frontal region. Dynamic facial emotions were associated with changes in SSVEP response within the temporal region, which are proposed to index inhibitory processing. It is suggested that static images represent non-canonical stimuli which are processed via different mechanisms to their more ecologically valid dynamic counterparts.

Demographics and survivial of a cohort of blood and breast cancer patients who developed heart failure following cancer treatment

Background/Aim: Cardiotoxicity resulting in heart failure is a devastating complication of cancer therapy. It is possible that a patient may survive cancer only to develop heart failure (HF), which is more deadly than cancer. The aim of this project was to profile the characteristics of patients at risk of cancer treatment induced heart failure. Methods: Linked Health Data Analysis of Queensland Cancer Registry (QCR) from 1996-2009, Death Registry and Hospital Administration records for HF and chemotherapy admissions were reviewed. Index heart failure admission must have occurred after the date of cancer registry entry. Results: A total of 15,987 patients were included in this analysis; 1,062 (6.6%) had chemotherapy+HF admission (51.4% Female) and 14,925 (93.4%) chemotherapy_no HF admission. Median age of chemotherapy+HF patients was 67 years (IQR 58 to 75) vs. 54 years (IQR 44 to 64) for chemotherapy_no HF admission. Chemotherapy+HF patients had increased risk of all cause mortality (HR 2.79 [95% CI 2.58-3.02] and 1.67 [95% CI, 1.54 to 1.81] after adjusting for age, sex, marital status, country of birth, cancer site and chemotherapy dose). Index HF admission occurred within one year of cancer diagnosis in 47% of HF patients with 80% of patinets having there index admission with 3 years. The number of chemotherapy cycles was not associated with significant reduction in survival time in chemotherapy+HF patients. Mean survival for heart failure patients was 5.3 years (95% CI, 4.99 - 5.62) vs.9.57 years (95% CI, 9.47-9.68) for chemotherapy_no HF admission patients. Conclusion: All-cause mortality was 67% higher in patients diagnosed with HF following chemotherapy in adjusted analysis for covariates. Methods to improve and better coordinate of the interdisciplinary care for cancer patients with HF involving cardiologists and oncologists are required, including evidence-based guidelines for the comprehensive assessment, monitoring and management of this cohort.

A new ambiguity acceptance test threshold determination method with controllable failure rate

The ambiguity acceptance test is an important quality control procedure in high precision GNSS data processing. Although the ambiguity acceptance test methods have been extensively investigated, its threshold determine method is still not well understood. Currently, the threshold is determined with the empirical approach or the fixed failure rate (FF-) approach. The empirical approach is simple but lacking in theoretical basis, while the FF-approach is theoretical rigorous but computationally demanding. Hence, the key of the threshold determination problem is how to efficiently determine the threshold in a reasonable way. In this study, a new threshold determination method named threshold function method is proposed to reduce the complexity of the FF-approach. The threshold function method simplifies the FF-approach by a modeling procedure and an approximation procedure. The modeling procedure uses a rational function model to describe the relationship between the FF-difference test threshold and the integer least-squares (ILS) success rate. The approximation procedure replaces the ILS success rate with the easy-to-calculate integer bootstrapping (IB) success rate. Corresponding modeling error and approximation error are analysed with simulation data to avoid nuisance biases and unrealistic stochastic model impact. The results indicate the proposed method can greatly simplify the FF-approach without introducing significant modeling error. The threshold function method makes the fixed failure rate threshold determination method feasible for real-time applications.

Dynamic digital posters : making the most of collaborative learning spaces

Academic and professional staff at Queensland University of Technology (QUT) have been faced with the challenge of how to create engaging student experiences in collaborative learning spaces. In 2013 a new Bachelor of Science course was implemented focusing on inquiry-based, collaborative and active learning. Student groups in two of the first year units carried out a poster assessment task. This paper provides a preliminary evaluation of the assessment approach used, whereby students created dynamic digital posters to capitalise on the affordances of the learning space.

Numerical investigation of deformation and failure mechanisms of osteopontin-hydroxyapatite interfaces and mineralized collagen fibril arrays

This thesis is a comprehensive study of deformation and failure mechanisms in bone at nano- and micro-scale levels. It explores the mechanical behaviour of osteopontin-hydroxyapatite interfaces and mineralized collagen fibril arrays, through atomistic molecular dynamics and finite element simulations. This thesis shows some main factors contributing to the excellent material properties of bone and provides some guidelines for development of new artificial biological materials and medical implants.

Identifying influential users of micro-blogging services : a dynamic action-based network approach

In this paper, we present a dynamic model to identify influential users of micro-blogging services. Micro-blogging services, such as Twitter, allow their users (twitterers) to publish tweets and choose to follow other users to receive tweets. Previous work on user influence on Twitter, concerns more on following link structure and the contents user published, seldom emphasizes the importance of interactions among users. We argue that, by emphasizing on user actions in micro-blogging platform, user influence could be measured more accurately. Since micro-blogging is a powerful social media and communication platform, identifying influential users according to user interactions has more practical meanings, e.g., advertisers may concern how many actions – buying, in this scenario – the influential users could initiate rather than how many advertisements they spread. By introducing the idea of PageRank algorithm, innovatively, we propose our model using action-based network which could capture the ability of influential users when they interacting with micro-blogging platform. Taking the evolving prosperity of micro-blogging into consideration, we extend our actionbaseduser influence model into a dynamic one, which could distinguish influential users in different time periods. Simulation results demonstrate that our models could support and give reasonable explanations for the scenarios that we considered.

Meeting the nutrition challenge of stage 3 renal failure : considerations for nursing practice

Self-care management is needed for effective management of chronic kidney disease. The main aim for treatment or management of chronic kidney disease is to delay the worsening of kidney function, and to prevent or to manage the co-morbidities. Selfcare management is not easy, and patients will face many challenges, especially when they cannot get use to the new treatment plan. One of the challenges they face is dietary restriction, which is a very important aspect in any self-care management programme. Chronic kidney disease patients require a low-protein, low-sodium, low-potassium, and low-phosphorus diet. There are several strategies patients can undertake to ensure adherence, such as self-monitoring their dietary habits and type of food consumed using a food diary; involving social support, such as family members and spouse to help them to adhere to their diet restrictions; setting goals and providing positive reinforcement when they achieved the targeted goals; joining self-management programmes to equip themselves with the necessary skills so that they can better adhere to the treatment regimes, including diet restriction; and lastly, having the knowledge about their regime, and using this knowledge to help them understand and improve their adherence.