Coronary microvascular ischemia in hypertrophic cardiomyopathy - a pixel-wise quantitative cardiovascular magnetic resonance perfusion study.

BACKGROUND: Microvascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness. METHODS: CMR perfusion imaging was undertaken during adenosine-induced hyperemia and again at rest in 35 patients together with late gadolinium enhancement (LGE) imaging. Myocardial blood flow (MBF) was quantified on a pixel-by-pixel basis from CMR perfusion images using a Fermi-constrained deconvolution algorithm. Regions-of-interest (ROI) in hypoperfused and hyperemic myocardium were identified from the MBF pixel maps. The myocardium was also divided into 16 AHA segments. RESULTS: Resting MBF was significantly higher in the endocardium than in the epicardium (mean ± SD: 1.25 ± 0.35 ml/g/min versus 1.20 ± 0.35 ml/g/min, P < 0.001), a pattern that reversed with stress (2.00 ± 0.76 ml/g/min versus 2.36 ± 0.83 ml/g/min, P < 0.001). ROI analysis revealed 11 (31%) patients with stress MBF lower than resting values (1.05 ± 0.39 ml/g/min versus 1.22 ± 0.36 ml/g/min, P = 0.021). There was a significant negative association between hyperemic MBF and wall thickness (β = −0.047 ml/g/min per mm, 95% CI: −0.057 to −0.038, P < 0.001) and a significantly lower probability of fibrosis in a segment with increasing hyperemic MBF (odds ratio per ml/g/min: 0.086, 95% CI: 0.078 to 0.095, P = 0.003). CONCLUSIONS: Pixel-wise quantitative CMR perfusion imaging identifies a subgroup of patients with HCM that have localised severe microvascular dysfunction which may give rise to myocardial ischemia

Comparison of the solophenyl-red polarization method and the immunohistochemical analysis for collagen type III

In the present study, we have compared the staining pattern of the Solophenyl-Red 3 BL-method for the visualization of collagen type III with the immunohistochemical staining in serial sections from 7 skin wounds (wound age 3 days up to 4 weeks) to elucidate the specifity of the histochemical staining method. Large amounts of collagen type III were clearly detectable in the investigated wounds using the immunohistochemical technique. In the sections stained with Solophenyl-Red, however, only 3 out of 7 skin lesions showed a significant positive red staining at the wound margin or in the granulation tissue, while the adjacent normal connective tissue revealed a typical intensive staining. Using polarization microscopy no characteristic bright green fibrils, as reported for collagen type 111, could be seen in the wound areas without positive Solophenyl-Red staining. Since the localization of collagen type III detected by immunohistochemistry and the presumed distribution of this collagen type by the Solophenyl-Red method was not identical, the histochemical polarization method has to be regarded as non-specific for visualization of this collagen type

Measuring the unmeasurable? A method to quantify adoption of integrated pest management practices in temperate arable farming systems

BACKGROUND: The impetus to adopt integrated pest management (IPM) practices has re-emerged in the last decade, mainly as a result of legislative and environmental drivers. However a significant deficit exists in the ability to practically monitor and measure IPM adoption across arable farms; therefore the aim of the project reported here was to establish a universal metric for quantifying adoption of IPM in temperate arable farming. This was achieved by: (a) identifying a set of key activities that contribute to IPM; (b) weighting these in terms of their importance to the achievement of IPM using panels of expert stakeholders in order to create the metric (scoring system from 0-100 indicating level of IPM practiced); (c) surveying arable farmers in the UK and Ireland about their pest management practices; and (d) measuring level of farmer adoption of IPM using the new metric. RESULTS. This new metric was found to be based on a consistent conception of IPM between countries and professional groups. The survey results showed that, while level of adoption of IPM practices varied over the sample, all farmers had adopted IPM to some extent (minimum 27.2 points, mean score of 65.1), but only 13 of 225 farmers (5.8%) had adopted more than 85% of what is theoretically possible, as measured by the new metric. CONCLUSION. We believe that this new metric would be a viable and cost-effective system to use to facilitate the benchmarking and monitoring of national IPM programmes in temperate zone countries with large scale arable farming systems

Neural Decision Boundaries for Maximal Information Transmission

We consider here how to separate multidimensional signals into two categories, such that the binary decision transmits the maximum possible information transmitted about those signals. Our motivation comes from the nervous system, where neurons process multidimensional signals into a binary sequence of responses (spikes). In a small noise limit, we derive a general equation for the decision boundary that locally relates its curvature to the probability distribution of inputs. We show that for Gaussian inputs the optimal boundaries are planar, but for non-Gaussian inputs the curvature is nonzero. As an example, we consider exponentially distributed inputs, which are known to approximate a variety of signals from natural environment.Comment: 5 pages, 3 figure

Transportability of Overall Survival Estimates From US to Canadian Patients With Advanced Non-Small Cell Lung Cancer With Implications for Regulatory and Health Technology Assessment.

IMPORTANCE: The external validity of survival outcomes derived from clinical practice data from US patients with advanced non-small cell lung cancer (NSCLC) is not known and is of potential importance because it may be used to support regulatory decision-making and health technology assessment outside of the US. OBJECTIVE: To evaluate whether overall survival (OS) estimates for a selected group of patients with advanced NSCLC from a large US clinical practice database are transportable to Canadian patients receiving the same systemic therapies. DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter cohort study used transportability analysis to assess whether adjustment for pretreatment characteristics of eligible patient cohorts could reliably approximate OS estimated from US-based samples to Canadian populations. A total of 17 432 eligible adult patients who were diagnosed de novo with advanced NSCLC on or after January 1, 2011, were included in the analysis and followed up until September 30, 2020. Because data on race and ethnicity were available in the US database but not the Canadian database and because racial and ethnic distribution was likely to be similar between US and Canadian patients, these characteristics were not analyzed. EXPOSURES: Initiation of platinum-doublet chemotherapy or pembrolizumab monotherapy as first-line systemic treatment for advanced NSCLC. MAIN OUTCOMES AND MEASURES: OS measured from the time of initiation of the respective treatment regimen. RESULTS: Among 17 432 eligible patients, 15 669 patients from the US and 1763 patients from Canada were included in the analysis. Of those, 11 863 patients (sample size-weighted estimates of mean [SD] age, 68.0 [9.3] years; 6606 [55.7%] male; 10 100 from the US and 1763 from Canada) were included in the subset of patients with complete data for baseline covariates. A total of 13 532 US patients received first-line chemotherapy, and 2137 received first-line pembrolizumab monotherapy. Of those, 8447 patients (62.4%) in the first-line chemotherapy group and 1653 patients (77.3%) in the first-line pembrolizumab group had complete data on baseline covariates for outcome model estimation. A total of 1476 Canadian patients who received first-line chemotherapy and 287 patients who received first-line pembrolizumab monotherapy were identified from the target population. After standardization to baseline patient covariates in the Canadian cohorts, transported OS estimates revealed a less than 5% mean absolute difference from the observed OS in the target population (0.56% over 60 months of follow-up in the first-line chemotherapy group and 4.54% over 30 months of follow-up in the first-line pembrolizumab group). Negative control analysis using a mismatched outcome model revealed a 6.64% discrepancy and an incompatible survival curve shape. The results were robust to assumptions of random missingness for baseline covariates, to unadjusted differences in baseline metastases and comorbidities, and to differences in the standard of care between the US and Canada related to administration of second-line anti-programmed cell death 1 ligand 1 immunotherapy for patients who initiated first-line chemotherapy. CONCLUSIONS AND RELEVANCE: The results of this cohort study suggest that, under specific circumstances, OS estimates from US clinical practice data can be adjusted using baseline clinical characteristics to closely approximate OS in selected groups of Canadian patients with advanced NSCLC. These results may have implications for regulatory decision-making and health technology assessment in target populations outside of the US

A Novel Ultrasonic Method for Accurate Characterization of Microstructural Gradients in Monolithic and Composite Tubular Structures

Prior studies have shown that ultrasonic velocity/time-of-flight imaging that uses back surface echo reflections to gauge volumetric material quality is well suited (perhaps more so than is the commonlyused peak amplitude c-scanning) for quantitative characterization of microstructural gradients. Such gradients include those due to pore fraction, density, fiber fraction, and chemical composition variations [11–15]. Variations in these microstructural factors can affect the uniformity of physical performance (including mechanical [stiffness, strength], thermal [conductivity], and electrical [conductivity, superconducting transition temperature], etc. performance) of monolithic and composite [1,3,6,12]. A weakness of conventional ultrasonic velocity/time-of-flight imaging (as well as to a lesser extent ultrasonic peak amplitude c-scanning where back surface echoes are gated [17] is that the image shows the effects of thickness as well as microstructural variations unless the part is uniformly thick. This limits this type of imaging’s usefulness in practical applications. The effect of thickness is easily observed from the equation for pulse-echo waveform time-of-flight (2τ) between the first front surface echo (FS) and the first back surface echo (B1), or between two successive back surface echoes where: 2τ=(2d)V (1) where d is the sample thickness and V is the velocity of ultrasound in the material. Interpretation of the time-of-flight image is difficult as thickness variation effects can mask or overemphasize the true microstructural variation portrayed in the image of a part containing thickness variations. Thickness effects on time-of-flight can also be interpreted by rearranging equation (1) to calculate velocity: V=(2d)2τ (2) such that velocity is inversely proportional to time-of-flight. Velocity and time-of-flight maps will be affected similarly (although inversely in terms of magnitude) by thickness variations, and velocity maps are used in this investigation to indicate time-of-flight variations.</p

Apheresis as novel treatment for refractory angina with raised lipoprotein(a): a randomised controlled trial

Aims To determine the clinical impact of lipoprotein apheresis in patients with refractory angina and raised lipoprotein(a) > 500 mg/L on the primary end point of quantitative myocardial perfusion, as well as secondary end points including atheroma burden, exercise capacity, symptoms, and quality of life. Methods We conducted a single-blinded randomized controlled trial in 20 patients with refractory angina and raised lipoprotein(a) > 500 mg/L, with 3 months of blinded weekly lipoprotein apheresis or sham, followed by crossover. The primary endpoint was change in quantitative myocardial perfusion reserve (MPR) assessed by cardiovascular magnetic resonance. Secondary endpoints included measures of atheroma burden, exercise capacity, symptoms and quality of life. Results The primary endpoint, namely MPR, increased following apheresis (0.47; 95% CI 0.31–0.63) compared with sham (−0.16; 95% CI − 0.33–0.02) yielding a net treatment increase of 0.63 (95% CI 0.37–0.89; P < 0.001 between groups). Improvements with apheresis compared with sham also occurred in atherosclerotic burden as assessed by total carotid wall volume (P < 0.001), exercise capacity by the 6 min walk test (P = 0.001), 4 of 5 domains of the Seattle angina questionnaire (all P < 0.02) and quality of life physical component summary by the short form 36 survey (P = 0.001). Conclusion Lipoprotein apheresis may represent an effective novel treatment for patients with refractory angina and raised lipoprotein(a) improving myocardial perfusion, atheroma burden, exercise capacity and symptoms

A 3D computed tomography based tool for orthopedic surgery planning

Series : Lecture notes in computational vision and biomechanics, vol. 19The preparation of a plan is essential for a surgery to take place in the best way possible and also for shortening patient’s recovery times. In the orthopedic case, planning has an accentuated significance due to the close relation between the degree of success of the surgery and the patient recovering time. It is important that surgeons are provided with tools that help them in the planning task, in order to make it more reliable and less time consuming. In this paper, we present a 3D Computed Tomography based solution and its implementation as an OsiriX plugin for orthopedic surgery planning. With the developed plugin, the surgeon is able to manipulate a three-dimensional isosurface rendered from the selected imaging study (a CT scan). It is possible to add digital representations of physical implants (surgical templates), in order to evaluate the feasibility of a plan. These templates are STL files generated from CAD models. There is also the feature to extract new isosurfaces of different voxel values and slice the final 3D model according to a predefined plane, enabling a 2D analysis of the planned solution. Finally, we discuss how the proposed application assists the surgeon in the planning process in an alternative way, where it is possible to three-dimensionally analyze the impact of a surgical intervention on the patient.(undefined