Effects of cardiac growth on electrical dyssynchrony in the single ventricle patient.

Single ventricle patients, including those with hypoplastic left heart syndrome (HLHS), typically undergo three palliative heart surgeries culminating in the Fontan procedure. HLHS is associated with high rates of morbidity and mortality, and many patients develop arrhythmias, electrical dyssynchrony, and eventually ventricular failure. However, the correlation between ventricular enlargement and electrical dysfunction in HLHS physiology remains poorly understood. Here we characterize the relationship between growth and electrophysiology in HLHS using computational modeling. We integrate a personalized finite element model, a volumetric growth model, and a personalized electrophysiology model to perform controlled in silico experiments. We show that right ventricle enlargement negatively affects QRS duration and interventricular dyssynchrony. Conversely, left ventricle enlargement can partially compensate for this dyssynchrony. These findings have potential implications on our understanding of the origins of electrical dyssynchrony and, ultimately, the treatment of HLHS patients.

Exploring current undergraduate student perspectives on the introduction of the degree apprenticeship scheme in diagnostic radiography - a single institution study.

INTRODUCTION: The first degree apprenticeship programme in diagnostic radiography was launched in March 2020. This route into radiography runs in parallel with 'conventional' pre-registration programmes where students apply to a higher education institution (HEI) and undertake discrete clinical placements. The aim of this study was to explore the perspectives of pre-registration students on the diagnostic radiographer degree apprenticeship route. METHODS: A qualitative approach (online questionnaire) gathered attitudes and opinions of pre-registration students from a single HEI, regarding the degree apprenticeship programme. Participants were pre-registration medical imaging students from all stages of the programme (n = 204). Braun and Clarks's thematic analysis was employed for data analysis. RESULTS: A response rate of 21% (n = 44) was recorded. Four themes emerged from data analysis: (1) misunderstandings surrounding the degree apprenticeship, (2) financial implications and (3) practical experience associated with both degree courses and (4) the experience the pre-registration degree has to offer. CONCLUSION: There was an apparent lack of understanding regarding the degree apprenticeship leading students to misinterpret aspects of the course. Additionally, students highlighted the earning aspect of the apprenticeship to be an advantage in comparison to student debts associated with the traditional pre-registration programmes. Furthermore, students emphasised the advantage of the clinical focus practice associated with the degree apprenticeship. Nevertheless, students who have selected the HEI route still value what the traditional pre-registration degree offers. IMPLICATIONS FOR PRACTICE: As degree apprenticeship programmes become widely available, a greater awareness should, therefore, follow. In the interim, there is scope for HEIs to seek to raise awareness of degree apprenticeship provision. HEIs should seek to allay any concerns and highlight the benefits of having this alternative route into the profession.

Psoriasis treat to target: defining outcomes in psoriasis using data from a real-world, population-based cohort study (the British Association of Dermatologists Biologics and Immunomodulators Register, BADBIR).

BACKGROUND: The 'treat to target' paradigm improves outcomes and reduces costs in chronic disease management but is not yet established in psoriasis. OBJECTIVES: To identify treatment targets in psoriasis using two common measures of disease activity: Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA). METHODS: Data from a multicentre longitudinal U.K. cohort of patients with psoriasis receiving systemic or biologic therapies (British Association of Dermatologists Biologics and Immunomodulators Register, BADBIR) were used to identify absolute PASI thresholds for 90% (PASI 90) and 75% (PASI 75) improvements in baseline disease activity, using receiver operating characteristic curves. The relationship between PGA (clear, almost clear, mild, moderate, moderate-severe, severe) and PASI (range 0-72) was described, and the concordance between absolute and relative definitions of response was determined. The same approach was used to establish treatment response and eligibility definitions based on PGA. RESULTS: Data from 13 422 patients were available (58% male, 91% white ethnicity, mean age 44·9 years), including over 23 000 longitudinal PASI and PGA scores. An absolute PASI ≤ 2 was concordant with PASI 90 and an absolute PASI ≤ 4 was concordant with PASI 75 in 90% and 88% of cases, respectively. These findings were robust to subgroups of timing of assessment, baseline disease severity and treatment modality. PASI and PGA were strongly correlated (Spearman's rank correlation coefficient 0·92). The median PASI increased from 0 (interquartile range 0-0, range 0-23) to 19 (interquartile range 15-25, range 0-64) for PGA clear to severe, respectively. PGA clear/almost clear was concordant with PASI ≤ 2 in 90% of cases, and PGA moderate-severe severe was concordant with the National Institute for Health and Care Excellence PASI eligibility criteria for biologics in 81% of cases. CONCLUSIONS: An absolute PASI ≤ 2 and PGA clear/almost clear represent relevant disease end points to inform treat-to-target management strategies in psoriasis. What's already known about this topic? The most commonly used relative disease activity measure in psoriasis is ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90); however, it has several limitations including dependency on a baseline severity assessment. Defining an absolute target disease activity end point in psoriasis has the potential to improve patient outcomes and reduce costs, as demonstrated by treat-to-target approaches in other chronic diseases such as hypertension and diabetes. The Physician's Global Assessment (PGA) is a popular alternative measure of psoriasis severity in daily practice; however, its utility has not been formally assessed with respect to PASI. What does this study add? An absolute PASI ≤ 2 corresponds with PASI 90 response and is a relevant disease end point for treat-to-target approaches in psoriasis. There is a strong correlation between PASI and PGA. PGA moderate-severe/severe may serve as an alternative eligibility criterion for biologics to PASI-based definitions, and PGA clear/almost clear is an appropriate alternative absolute treatment end point. What are the clinical implications of this work? Absolute PASI ≤ 2 and PGA clear/almost clear represent relevant disease end points to inform treat-to-target management strategies in psoriasis.

Identifying demographic, social and clinical predictors of biologic therapy effectiveness in psoriasis: a multicentre longitudinal cohort study.

BACKGROUND: Biologic therapies have revolutionized the treatment of moderate-to-severe psoriasis. However, for reasons largely unknown, many patients do not respond or lose response to these drugs. OBJECTIVES: To evaluate demographic, social and clinical factors that could be used to predict effectiveness and stratify response to biologic therapies in psoriasis. METHODS: Using a multicentre, observational, prospective pharmacovigilance study (BADBIR), we identified biologic-naive patients starting biologics with outcome data at 6 (n = 3079) and 12 (n = 3110) months. Associations between 31 putative predictors and outcomes were investigated in univariate and multivariable regression analyses. Potential stratifiers of treatment response were investigated with statistical interactions. RESULTS: Eight factors associated with reduced odds of achieving ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) at 6 months were identified (described as odds ratio and 95% confidence interval): demographic (female sex, 0·78, 0·66-0·93); social (unemployment, 0·67, 0·45-0·99); unemployment due to ill health (0·62, 0·48-0·82); ex- and current smoking (0·81, 0·66-0·99 and 0·79, 0·63-0·99, respectively); clinical factors (high weight, 0·99, 0·99-0·99); psoriasis of the palms and/or soles (0·75, 0·61-0·91); and presence of small plaques only compared with small and large plaques (0·78, 0·62-0·96). White ethnicity (1·48, 1·12-1·97) and higher baseline PASI (1·04, 1·03-1·04) were associated with increased odds of achieving PASI 90. The findings were largely consistent at 12 months. There was little evidence for predictors of differential treatment response. CONCLUSIONS: Psoriasis phenotype and potentially modifiable factors are associated with poor outcomes with biologics, underscoring the need for lifestyle management. Effect sizes suggest that these factors alone cannot inform treatment selection.

A generalized multi-resolution expansion for uncertainty propagation with application to cardiovascular modeling.

Computational models are used in a variety of fields to improve our understanding of complex physical phenomena. Recently, the realism of model predictions has been greatly enhanced by transitioning from deterministic to stochastic frameworks, where the effects of the intrinsic variability in parameters, loads, constitutive properties, model geometry and other quantities can be more naturally included. A general stochastic system may be characterized by a large number of arbitrarily distributed and correlated random inputs, and a limited support response with sharp gradients or event discontinuities. This motivates continued research into novel adaptive algorithms for uncertainty propagation, particularly those handling high dimensional, arbitrarily distributed random inputs and non-smooth stochastic responses. In this work, we generalize a previously proposed multi-resolution approach to uncertainty propagation to develop a method that improves computational efficiency, can handle arbitrarily distributed random inputs and non-smooth stochastic responses, and naturally facilitates adaptivity, i.e., the expansion coefficients encode information on solution refinement. Our approach relies on partitioning the stochastic space into elements that are subdivided along a single dimension, or, in other words, progressive refinements exhibiting a binary tree representation. We also show how these binary refinements are particularly effective in avoiding the exponential increase in the multi-resolution basis cardinality and significantly reduce the regression complexity for moderate to high dimensional random inputs. The performance of the approach is demonstrated through previously proposed uncertainty propagation benchmarks and stochastic multi-scale finite element simulations in cardiovascular flow.

On a sparse pressure-flow rate condensation of rigid circulation models.

Cardiovascular simulation has shown potential value in clinical decision-making, providing a framework to assess changes in hemodynamics produced by physiological and surgical alterations. State-of-the-art predictions are provided by deterministic multiscale numerical approaches coupling 3D finite element Navier Stokes simulations to lumped parameter circulation models governed by ODEs. Development of next-generation stochastic multiscale models whose parameters can be learned from available clinical data under uncertainty constitutes a research challenge made more difficult by the high computational cost typically associated with the solution of these models. We present a methodology for constructing reduced representations that condense the behavior of 3D anatomical models using outlet pressure-flow polynomial surrogates, based on multiscale model solutions spanning several heart cycles. Relevance vector machine regression is compared with maximum likelihood estimation, showing that sparse pressure/flow rate approximations offer superior performance in producing working surrogate models to be included in lumped circulation networks. Sensitivities of outlets flow rates are also quantified through a Sobol׳ decomposition of their total variance encoded in the orthogonal polynomial expansion. Finally, we show that augmented lumped parameter models including the proposed surrogates accurately reproduce the response of multiscale models they were derived from. In particular, results are presented for models of the coronary circulation with closed loop boundary conditions and the abdominal aorta with open loop boundary conditions.

Uncertainty quantification in virtual surgery hemodynamics predictions for single ventricle palliation.

The adoption of simulation tools to predict surgical outcomes is increasingly leading to questions about the variability of these predictions in the presence of uncertainty associated with the input clinical data. In the present study, we propose a methodology for full propagation of uncertainty from clinical data to model results that, unlike deterministic simulation, enables estimation of the confidence associated with model predictions. We illustrate this problem in a virtual stage II single ventricle palliation surgery example. First, probability density functions (PDFs) of right pulmonary artery (PA) flow split ratio and average pulmonary pressure are determined from clinical measurements, complemented by literature data. Starting from a zero-dimensional semi-empirical approximation, Bayesian parameter estimation is used to find the distributions of boundary conditions that produce the expected PA flow split and average pressure PDFs as pre-operative model results. To reduce computational cost, this inverse problem is solved using a Kriging approximant. Second, uncertainties in the boundary conditions are propagated to simulation predictions. Sparse grid stochastic collocation is employed to statistically characterize model predictions of post-operative hemodynamics in models with and without PA stenosis. The results quantify the statistical variability in virtual surgery predictions, allowing for placement of confidence intervals on simulation outputs.

Multimodal microscopy using 'half and half' contact mode and ultrasonic force microscopy.

Advances in the design and fabrication of multifunctional nanostructured materials require characterization techniques capable of simultaneously mapping multiple material properties with nanoscale resolution. We show that this can be achieved by combining nanomechanical information from ultrasonic force microscopy (UFM) with simultaneously acquired friction force and conductivity measurements from contact mode scanning. This utilizes a 'half and half' approach, where the AFM is operated alternatively in UFM and contact mode, with the switching rate sufficiently fast that simultaneous contact mode and UFM information is acquired at each pixel of an image. We demonstrate the potential of such a multimodal approach through its application to composite systems consisting of graphene islands on a copper surface, single-walled carbon nanotubes (SWNTs) on a silicon oxide substrate, and a graphene epoxy composite. The half and half approach enables the friction force to be measured without topographical cross-talk. Application to the SWNT sample reveals a further advantage; due to the superlubricity of UFM it enables standard contact mode imaging techniques to be applied to delicate samples.

Friction force microscopy: a simple technique for identifying graphene on rough substrates and mapping the orientation of graphene grains on copper.

At a single atom thick, it is challenging to distinguish graphene from its substrate using conventional techniques. In this paper we show that friction force microscopy (FFM) is a simple and quick technique for identifying graphene on a range of samples, from growth substrates to rough insulators. We show that FFM is particularly effective for characterizing graphene grown on copper where it can correlate the graphene growth to the three-dimensional surface topography. Atomic lattice stick-slip friction is readily resolved and enables the crystallographic orientation of the graphene to be mapped nondestructively, reproducibly and at high resolution. We expect FFM to be similarly effective for studying graphene growth on other metal/locally crystalline substrates, including SiC, and for studying growth of other two-dimensional materials such as molybdenum disulfide and hexagonal boron nitride.

Fluid-structure interaction simulations of the Fontan procedure using variable wall properties.

Children born with single ventricle heart defects typically undergo a staged surgical procedure culminating in a total cavopulmonary connection (TCPC) or Fontan surgery. The goal of this work was to perform physiologic, patient-specific hemodynamic simulations of two post-operative TCPC patients by using fluid-structure interaction (FSI) simulations. Data from two patients are presented, and post-op anatomy is reconstructed from MRI data. Respiration rate, heart rate, and venous pressures are obtained from catheterization data, and inflow rates are obtained from phase contrast MRI data and are used together with a respiratory model. Lumped parameter (Windkessel) boundary conditions are used at the outlets. We perform FSI simulations by using an arbitrary Lagrangian-Eulerian finite element framework to account for motion of the blood vessel walls in the TCPC. This study is the first to introduce variable elastic properties for the different areas of the TCPC, including a Gore-Tex conduit. Quantities such as wall shear stresses and pressures at critical locations are extracted from the simulation and are compared with pressure tracings from clinical data as well as with rigid wall simulations. Hepatic flow distribution and energy efficiency are also calculated and compared for all cases. There is little effect of FSI on pressure tracings, hepatic flow distribution, and time-averaged energy efficiency. However, the effect of FSI on wall shear stress, instantaneous energy efficiency, and wall motion is significant and should be considered in future work, particularly for accurate prediction of thrombus formation.

Virtual surgeries in patients with congenital heart disease: a multi-scale modelling test case.

The objective of this work is to perform a virtual planning of surgical repairs in patients with congenital heart diseases--to test the predictive capability of a closed-loop multi-scale model. As a first step, we reproduced the pre-operative state of a specific patient with a univentricular circulation and a bidirectional cavopulmonary anastomosis (BCPA), starting from the patient's clinical data. Namely, by adopting a closed-loop multi-scale approach, the boundary conditions at the inlet and outlet sections of the three-dimensional model were automatically calculated by a lumped parameter network. Successively, we simulated three alternative surgical designs of the total cavopulmonary connection (TCPC). In particular, a T-junction of the venae cavae to the pulmonary arteries (T-TCPC), a design with an offset between the venae cavae (O-TCPC) and a Y-graft design (Y-TCPC) were compared. A multi-scale closed-loop model consisting of a lumped parameter network representing the whole circulation and a patient-specific three-dimensional finite volume model of the BCPA with detailed pulmonary anatomy was built. The three TCPC alternatives were investigated in terms of energetics and haemodynamics. Effects of exercise were also investigated. Results showed that the pre-operative caval flows should not be used as boundary conditions in post-operative simulations owing to changes in the flow waveforms post-operatively. The multi-scale approach is a possible solution to overcome this incongruence. Power losses of the Y-TCPC were lower than all other TCPC models both at rest and under exercise conditions and it distributed the inferior vena cava flow evenly to both lungs. Further work is needed to correlate results from these simulations with clinical outcomes.

The influence of socioeconomic deprivation on outcomes following renal transplantation in the United kingdom.

Socio-economic deprivation is an important determinant of poor health and is associated with a higher incidence of end-stage renal disease, higher mortality for dialysis patients and lower chance of being listed for transplantation. The influence of deprivation on outcomes following renal transplantation has not previously been reported in the United Kingdom. The Welsh Index of Multiple Deprivation was used to assess the influence of socio-economic deprivation on outcomes for 621 consecutive renal transplant recipients from a single centre in the United Kingdom transplanted between 1997 and 2005. Outcomes measured were rate of acute rejection and graft survival. Patients from the most deprived areas were significantly more likely to experience an episode of acute rejection requiring treatment (36% vs. 27%, p=0.01) and increasing overall deprivation correlated with increasing rates of rejection (p=0.03). Income deprivation was significantly and independently associated with graft survival (HR 1.484, p=0.046). Among patients who experienced acute rejection 5-year graft survival was 79% for those from the most deprived areas compared with 90% for patients from the least deprived areas (p = 0.018). Overall socio-economic deprivation is associated with higher rate of acute rejection following renal transplantation and income deprivation is a significant and independent predictor of graft survival.

Statin-induced myopathy in the rat: relationship between systemic exposure, muscle exposure and myopathy.

Rare instances of myopathy are associated with all statins, but cerivastatin was withdrawn from clinical use due to a greater incidence of myopathy. The mechanism of statin-induced myopathy with respect to tissue disposition was investigated by measuring the systemic, hepatic, and skeletal muscle exposure of cerivastatin, rosuvastatin, and simvastatin in rats before and after muscle damage. The development of myopathy was not associated with the accumulation of statins in skeletal muscle. For each statin exposure was equivalent in muscles irrespective of their fibre-type sensitivity to myopathy. The low amount of each statin in skeletal muscle relative to the liver does not support a significant role for transporters in the disposition of statins in skeletal muscle. Finally, the concentration of cerivastatin necessary to cause necrosis in skeletal muscle was considerably lower than rosuvastatin or simvastatin, supporting the concept cerivastatin is intrinsically more myotoxic than other statins.

Optical spectroscopy on in vitro fungal diagnosis.

The growing incidence of microbial infections and the increasing ability of such organisms to acquire resistance to antimicrobial treatment lead the requirement of fast bacteria and fungi identification methods. In this work we explored optical spectroscopic techniques on fungal identification. We show that some fungal infections can be identified by ultraviolet optical excitation of fungi fluorescence followed by the spectral analysis of the emitted light. Moreover, we demonstrate that ultraviolet LED and LASER could be applied in fungal identification and a new device for fungal diagnosis is proposed.

Presentation, management, and outcome of out of hospital cardiopulmonary arrest: comparison by underlying aetiology.

OBJECTIVE: To describe and compare presentation, management, and survival by aetiology of cardiopulmonary arrest. DESIGN, SETTING, AND PATIENTS: A retrospective cohort study was undertaken of all 21 175 first out of hospital cardiopulmonary arrests in Scotland between May 1991 and March 1998. MAIN OUTCOME MEASURE: Discharge alive from hospital. RESULTS: Presumed cardiac disease accounted for 17 451 cases (82%), other internal aetiologies for 1814 (9%), and external aetiologies for 1910 (9%). Arrests caused by presumed cardiac disease had a better risk profile in terms of presence of a witness, bystander cardiopulmonary resuscitation, call-response interval, and use of defibrillation; 1265 (7%) of those who arrested from presumed cardiac disease were discharged alive, compared with only 77 (2%) of those with non-cardiac disorders (p < 0.001). Among those defibrillated, call-response interval was associated with survival following arrests from both presumed cardiac and non-cardiac causes (p < 0.001). CONCLUSIONS: Out of hospital cardiopulmonary arrests from non-cardiac causes were associated with worse crude survival than arrests from cardiac causes. Improvements in call-response interval and basic life support skills in the community would improve survival irrespective of the aetiology and should therefore be encouraged.

Survival from accidental strangulation from a scarf resulting in laryngeal rupture and carotid artery stenosis: the "Isadora Duncan syndrome". A case report and review of literature.

In 1929 the dancer Isadora Duncan died from strangulation and carotid artery insult when her scarf caught in the wheels of a motor vehicle in which she was travelling. As part of the Edinburgh Festival scene, cycle propelled rickshaws are in popular use as short range taxis. The case is presented of a student who sustained a laryngeal rupture from strangulation with a scarf in the same way as Isadora. Despite an out of hospital cardiorespiratory arrest, severe laryngeal trauma, and carotid artery damage resulting in hemiparesis, the patient was successfully resuscitated and recovered with no neurological deficit. It is believed that this is the first recorded survival from this condition.

Survivorship and growth of Fucus gardneri after transplant to an acid mine drainage-polluted area.

Acid mine drainage (AMD) from an abandoned copper mine at Britannia Beach, British Columbia, Canada, enters the marine environment through Britannia Creek. The surrounding intertidal zone is devoid of rockweed, Fucus gardneri Silva, a seaweed that dominates nearby shores. Rockweed plants were transplanted to the intertidal zone near Britannia Creek and monitored for changes in percent cover, survivorship, growth rate and Cu content. Autumn and winter transplants to within 100 m of Britannia Creek resulted in negative growth rates and high mortality within 57 days of exposure to AMD, with Cu levels in rockweed surpassing 2,300 ppm in dry tissue. Summer transplants to sites 300-700 m from Britannia Creek showed no consistent differences between AMD-exposed rockweed and control plants, possibly because the plants were stressed by desiccation. The results are consistent with ecological effects observed in other studies, and provide strong evidence for the role of AMD in excluding rockweed from the shores near Britannia Creek.

Flexible tubular replicas of abdominal aortic aneurysms.

The aim of this study was to manufacture life-size, flexible, tubular replicas of human abdominal aortic aneurysms and the associated vasculature, suitable for use in a training simulator for endovascular procedures. Selective laser sintering was used to create a geometrically correct master model for each of ten anatomical variations. The masters were used to generate flexible latex replicas. The use of the replicas in the training simulator was demonstrated. In total ten silicone rubber models were produced. When connected into the training simulator and perfused at arterial pressure it was possible to deploy an endovascular stent under fluoroscopic control and to perform angiography. The study has shown that conventional rapid prototyping technology can be used to manufacture flexible, radiolucent replicas which provide a realistic training environment for endovascular procedures.