THE CLINICAL IMPACT OF INTRAVASCULAR ULTRASOUND DERIVED VIRTUAL HISTOLOGY ON PERCUTANEOUS CORONARY INTERVENTION.

It has been shown that early interventional treatment of patients with high risk acute coronary syndromes (ACS) has a favourable effect on mortality. It is also known that coronary plaque rupture and atherothrombosis creates a mileu of necrotic and thrombotic material, which is difficult to treat. Moreover, angiographic assessment of coronary artery disease is highly flawed; 2-dimensional luminal silhouettes are not ideal templates to guide very important interventions. Intravascular ultrasound (IVUS) is the gold standard imaging tool able to delineate vessel dimensions, plaque burden, length and now with virtual histology (VH) - plaque composition. Despite optimal medical care and urgent revascularisation, 12-20% of ACS patients will suffer a further major adverse cardiac event (MACE) at 30 months. Our aim was to evaluate the angiographic treatment of high risk ACS patients by performing IVUS-VH pre and post-intervention, with the operators blinded to the images. Our hypotheses for this work were as follows: 1. Significant compositional and structural differences exist between culprit, non-culprit and stable plaques when analysed by Virtual Histology. 2. The histologically most unstable plaque does not occur at the site of maximum angiographic stenosis (in culprit lesions). 3. Angiographically guided stent length selection and positioning is flawed, leaving unstable plaque behind in the reference segments. Following recruitment, 135 lesions split into: 70 ACS culprit; 20 ACS non-culprit and 35 Stable lesions underwent analysis for inter-observer and intra-observer variability. We were able to show good standard markers of correlation but a large repeatability co-efficent, for some outputs from the analysis. This has raised questions with regard to the ability of the technique to detect differences between plaque types. In relation to our main hypothesis, we have been able to show structural and compositional volume differences between “active” ACS plaques (n=70) and “stable” angina plaques (n=35). We have used the most important of these to generate a plaque risk score based upon ROC statistics and logistic regression. The most important discriminators were: Remodelling index at the minimum lumen area; Plaque Burden; Presence of VH-TCFA; minimum lumen area (MLA) <4mm2 and necrotic core to dense calcium ratio (NC/DC). The subsequent risk model was tested on an independent, blinded cohort of plaques from the Thoraxcentre, Rotterdam (n=50). This confirmed good discriminatory power for the equation (AUC – 0.71). Within this hypothesis we also explored the differences in individual areas of plaque. At two separate sites (MLA and MAX NC) in each lesion type (ACS and stable) n=210, we showed that the MAX NC site lies proximal to the MLA in most cases and contains more positively remodelled plaque disease with less calcification. This is important as positively remodeled plaque disease is often not visible on a plain coronary angiogram when treating ACS lesions. Finally, as a follow on from thie previous chapter, we examined the treatment of ACS lesions by blinded IVUS examination. The operator completed their stent procedure with only angiographic guidance. We were able to show in 56 ACS lesions that systematic errors of judgement occur related to sizing of the vessel, the choice of stent sizes and the subsequent stent deployment. 36%, 40% and 65.5% of stents met three separate standard criteria for good stent deployment. Moreover, between 5-40% of stents had some form of significant abnormality. With regard to the sizing of stents to the vessel, the mean reference vessel size was 10.58mm2 (±2.51) yet the minimum stent area achieved was only 6.79mm2 (±2.43). If the stent that was chosen had been symmetrically deployed to its nominal size (e.g 2.5; 3.0; 3.5) then the stent area achievable should have been 8.87mm2 (±2.68). This has allowed us to calculate for the first time an estimated “under deployment area”. This was 2.08mm2 (±1.87)

Derivation of Suitability Metrics for Remote Access Mode Experiments

When considering the possible use of an online mode of experimentation it is important to evaluate the suitability of the remote access mode to a particular learning exercise. Within a large and diverse set of possible experiment-oriented learning exercises, it follows that not all laboratory experiments are well-suited for conversion to the remote access mode. In this paper we consider a range of factors that should be considered before the decision is taken to implement a remote laboratory. These factors fit broadly into four categories: learning factors, equipment factors, cohort factors and accreditation factors. Some of the factors may demonstrate a tendency to belong to more than one category, and some may present with a more significant weighting than others, but the categorical organization of the factors adds an ability to apply an objective assessment to remote access mode suitability

A circuit mechanism for decision-making biases and NMDA receptor hypofunction

Decision-making biases can be features of normal behaviour, or deficits underlying neuropsychiatric symptoms. We used behavioural psychophysics, spiking-circuit modelling and pharmacological manipulations to explore decision-making biases during evidence integration. Monkeys showed a pro-variance bias (PVB): a preference to choose options with more variable evidence. The PVB was also present in a spiking circuit model, revealing a potential neural mechanism for this behaviour. To model possible effects of NMDA receptor (NMDA-R) antagonism on this behaviour, we simulated the effects of NMDA-R hypofunction onto either excitatory or inhibitory neurons in the model. These were then tested experimentally using the NMDA-R antagonist ketamine, a pharmacological model of schizophrenia. Ketamine yielded an increase in subjects' PVB, consistent with lowered cortical excitation/inhibition balance from NMDA-R hypofunction predominantly onto excitatory neurons. These results provide a circuit-level mechanism that bridges across explanatory scales, from the synaptic to the behavioural, in neuropsychiatric disorders where decision-making biases are prominent

SimShiftDB; local conformational restraints derived from chemical shift similarity searches on a large synthetic database

We present SimShiftDB, a new program to extract conformational data from protein chemical shifts using structural alignments. The alignments are obtained in searches of a large database containing 13,000 structures and corresponding back-calculated chemical shifts. SimShiftDB makes use of chemical shift data to provide accurate results even in the case of low sequence similarity, and with even coverage of the conformational search space. We compare SimShiftDB to HHSearch, a state-of-the-art sequence-based search tool, and to TALOS, the current standard tool for the task. We show that for a significant fraction of the predicted similarities, SimShiftDB outperforms the other two methods. Particularly, the high coverage afforded by the larger database often allows predictions to be made for residues not involved in canonical secondary structure, where TALOS predictions are both less frequent and more error prone. Thus SimShiftDB can be seen as a complement to currently available methods

Determining the date of diagnosis – is it a simple matter? The impact of different approaches to dating diagnosis on estimates of delayed care for ovarian cancer in UK primary care

Background Studies of cancer incidence and early management will increasingly draw on routine electronic patient records. However, data may be incomplete or inaccurate. We developed a generalisable strategy for investigating presenting symptoms and delays in diagnosis using ovarian cancer as an example. Methods The General Practice Research Database was used to investigate the time between first report of symptom and diagnosis of 344 women diagnosed with ovarian cancer between 01/06/2002 and 31/05/2008. Effects of possible inaccuracies in dating of diagnosis on the frequencies and timing of the most commonly reported symptoms were investigated using four increasingly inclusive definitions of first diagnosis/suspicion: 1. "Definite diagnosis" 2. "Ambiguous diagnosis" 3. "First treatment or complication suggesting pre-existing diagnosis", 4 "First relevant test or referral". Results The most commonly coded symptoms before a definite diagnosis of ovarian cancer, were abdominal pain (41%), urogenital problems(25%), abdominal distension (24%), constipation/change in bowel habits (23%) with 70% of cases reporting at least one of these. The median time between first reporting each of these symptoms and diagnosis was 13, 21, 9.5 and 8.5 weeks respectively. 19% had a code for definitions 2 or 3 prior to definite diagnosis and 73% a code for 4. However, the proportion with symptoms and the delays were similar for all four definitions except 4, where the median delay was 8, 8, 3, 10 and 0 weeks respectively. Conclusion Symptoms recorded in the General Practice Research Database are similar to those reported in the literature, although their frequency is lower than in studies based on self-report. Generalisable strategies for exploring the impact of recording practice on date of diagnosis in electronic patient records are recommended, and studies which date diagnoses in GP records need to present sensitivity analyses based on investigation, referral and diagnosis data. Free text information may be essential in obtaining accurate estimates of incidence, and for accurate dating of diagnoses

Congenital anomalies in low- and middle-income countries: the unborn child of global surgery.

Surgically correctable congenital anomalies cause a substantial burden of global morbidity and mortality. These anomalies disproportionately affect children in low- and middle-income countries (LMICs) due to sociocultural, economic, and structural factors that limit the accessibility and quality of pediatric surgery. While data from LMICs are sparse, available evidence suggests that the true human and financial cost of congenital anomalies is grossly underestimated and that pediatric surgery is a cost-effective intervention with the potential to avert significant premature mortality and lifelong disability

A projective Dirac operator on CP^2 within fuzzy geometry

We propose an ansatz for the commutative canonical spin_c Dirac operator on CP^2 in a global geometric approach using the right invariant (left action-) induced vector fields from SU(3). This ansatz is suitable for noncommutative generalisation within the framework of fuzzy geometry. Along the way we identify the physical spinors and construct the canonical spin_c bundle in this formulation. The chirality operator is also given in two equivalent forms. Finally, using representation theory we obtain the eigenspinors and calculate the full spectrum. We use an argument from the fuzzy complex projective space CP^2_F based on the fuzzy analogue of the unprojected spin_c bundle to show that our commutative projected spin_c bundle has the correct SU(3)-representation content.Comment: reduced to 27 pages, minor corrections, minor improvements, typos correcte

A critical analysis of building sustainability assessment methods for healthcare buildings

The healthcare building project contains different aspects from the most common projects. Designing a healthcare environment is based on a number of criteria related to the satisfaction and well-being of the professional working teams, patients and administrators. Mostly due to various design requirements, these buildings are rarely designed and operated in a sustainable way. Therefore, the sustainable development is a concept whose importance has grown significantly in the last decade in this sector. The worldwide economic crisis reinforces the growing environmental concerns as well as raising awareness among people to a necessary and inevitable shift in the values of their society. To support sustainable building design, several building sustainability assessment (BSA) methods are being developed worldwide. Since healthcare buildings are rather complex systems than other buildings, so specific methods were developed for them. These methods are aimed to support decision-making towards the introduction of the best sustainability practices during the design and operation phases of a healthcare environment. However, the comparison between the results of different methods is difficult, if not impossible, since they address different environmental, societal and economic criteria, and they emphasize different phases of the life cycle. Therefore, the aim of this study was to clarify the differences between the main BSA methods for healthcare buildings by analysing and categorizing them. Furthermore, the benefits of these methods in promoting a more sustainable environment will be analysed, and the current situation of them within the context of standardization of the concept sustainable construction will be discussed.The authors acknowledge the Portuguese Foundation for Science and Technology and POPH/FSE for the financial support for this study under the Reference SFRH/BD/77959/2011

Flow through a circular tube with a permeable Navier slip boundary

For Newtonian fluid flow in a right circular tube, with a linear Navier slip boundary, we show that a second flow field arises which is different to conventional Poiseuille flow in the sense that the corresponding pressure is quadratic in its dependence on the length along the tube, rather than a linear dependence which applies for conventional Poiseuille flow. However, assuming that the quadratic pressure is determined, say from known experimental data, then the new solution only exists for a precisely prescribed permeability along the boundary. While this cannot occur for conventional pipe flow, for fluid flow through carbon nanotubes embedded in a porous matrix, it may well be an entirely realistic possibility, and could well explain some of the high flow rates which have been reported in the literature. Alternatively, if the radial boundary flow is prescribed, then the new flow field exists only for a given quadratic pressure. Our primary purpose here is to demonstrate the existence of a new pipe flow field for a permeable Navier slip boundary and to present a numerical solution and two approximate analytical solutions. The maximum flow rate possible for the new solution is precisely twice that for the conventional Poiseuille flow, which occurs for constant inward directed flow across the boundary

Effective suckling in relation to naked maternal-infant body contact in the first hour of life: an observation study

Background Best practice guidelines to promote breastfeeding suggest that (i) mothers hold their babies in naked body contact immediately after birth, (ii) babies remain undisturbed for at least one hour and (iii) breastfeeding assistance be offered during this period. Few studies have closely observed the implementation of these guidelines in practice. We sought to evaluate these practices on suckling achievement within the first hour after birth. Methods Observations of seventy-eight mother-baby dyads recorded newborn feeding behaviours, the help received by mothers and birthing room practices each minute, for sixty minutes. Results Duration of naked body contact between mothers and their newborn babies varied widely from 1 to 60 minutes, as did commencement of suckling (range = 10 to 60 minutes). Naked maternal-infant body contact immediately after birth, uninterrupted for at least thirty minutes did not predict effective suckling within the first hour of birth. Newborns were four times more likely to sustain deep rhythmical suckling when their chin made contact with their mother’s breast as they approached the nipple (OR 3.8; CI 1.03 - 14) and if their mothers had given birth previously (OR 6.7; CI 1.35 - 33). Infants who had any naso-oropharyngeal suctioning administered at birth were six times less likely to suckle effectively (OR .176; CI .04 - .9). Conclusion Effective suckling within the first hour of life was associated with a collection of practices including infants positioned so their chin can instinctively nudge the underside of their mother’s breast as they approach to grasp the nipple and attach to suckle. The best type of assistance provided in the birthing room that enables newborns to sustain an effective latch was paying attention to newborn feeding behaviours and not administering naso-oropharyngeal suction routinely