Quantitative magnetic resonance image analysis via the EM algorithm with stochastic variation

Quantitative Magnetic Resonance Imaging (qMRI) provides researchers insight into pathological and physiological alterations of living tissue, with the help of which researchers hope to predict (local) therapeutic efficacy early and determine optimal treatment schedule. However, the analysis of qMRI has been limited to ad-hoc heuristic methods. Our research provides a powerful statistical framework for image analysis and sheds light on future localized adaptive treatment regimes tailored to the individual's response. We assume in an imperfect world we only observe a blurred and noisy version of the underlying pathological/physiological changes via qMRI, due to measurement errors or unpredictable influences. We use a hidden Markov random field to model the spatial dependence in the data and develop a maximum likelihood approach via the Expectation--Maximization algorithm with stochastic variation. An important improvement over previous work is the assessment of variability in parameter estimation, which is the valid basis for statistical inference. More importantly, we focus on the expected changes rather than image segmentation. Our research has shown that the approach is powerful in both simulation studies and on a real dataset, while quite robust in the presence of some model assumption violations.Comment: Published in at http://dx.doi.org/10.1214/07-AOAS157 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Longitudinal image analysis of tumour–healthy brain change in contrast uptake induced by radiation

The work is motivated by a quantitative magnetic resonance imaging study of the differential tumour–healthy tissue change in contrast uptake induced by radiation. The goal is to determine the time in which there is maximal contrast uptake (a surrogate for permeability) in the tumour relative to healthy tissue. A notable feature of the data is its spatial heterogeneity. Zhang and co-workers have discussed two parallel approaches to ‘denoise’ a single image of change in contrast uptake from baseline to one follow-up visit of interest. In this work we extend the image model to explore the longitudinal profile of the tumour–healthy tissue contrast uptake in multiple images over time. We fit a two-stage model. First, we propose a longitudinal image model for each subject. This model simultaneously accounts for the spatial and temporal correlation and denoises the observed images by borrowing strength both across neighbouring pixels and over time. We propose to use the Mann–Whitney U -statistic to summarize the tumour contrast uptake relative to healthy tissue. In the second stage, we fit a population model to the U -statistic and estimate when it achieves its maximum. Our initial findings suggest that the maximal contrast uptake of the tumour core relative to healthy tissue peaks around 3 weeks after initiation of radiotherapy, though this warrants further investigation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79255/1/j.1467-9876.2010.00718.x.pd

Inequity in access to transplantation in the UK

Background and objectives Despite the presence of a universal health care system, it is unclear if there is intercenter variation in access to kidney transplantation in the United Kingdom. This study aims to assess whether equity exists in access to kidney transplantation in the United Kingdom after adjustment for patient-specific factors and center practice patterns. Design, setting, participants, & measurements In this prospective, observational cohort study including all 71 United Kingdom kidney centers, incident RRT patients recruited between November 2011 and March 2013 as part of the Access to Transplantation and Transplant Outcome Measures study were analyzed to assess preemptive listing (n=2676) and listing within 2 years of starting dialysis (n=1970) by center. Results Seven hundred and six participants (26%) were listed preemptively, whereas 585 (30%) were listed within 2 years of commencing dialysis. The interquartile range across centers was 6%–33% for preemptive listing and 25%–40% for listing after starting dialysis. Patient factors, including increasing age, most comorbidities, body mass index >35 kg/m2, and lower socioeconomic status, were associated with a lower likelihood of being listed and accounted for 89% and 97% of measured intercenter variation for preemptive listing and listing within 2 years of starting dialysis, respectively. Asian (odds ratio, 0.49; 95% confidence interval, 0.33 to 0.72) and Black (odds ratio, 0.43; 95% confidence interval, 0.26 to 0.71) participants were both associated with reduced access to preemptive listing; however Asian participants were associated with a higher likelihood of being listed after starting dialysis (odds ratio, 1.42; 95% confidence interval, 1.12 to 1.79). As for center factors, being registered at a transplanting center (odds ratio, 3.1; 95% confidence interval, 2.36 to 4.07) and a universal approach to discussing transplantation (odds ratio, 1.4; 95% confidence interval, 1.08 to 1.78) were associated with higher preemptive listing, whereas using a written protocol was associated negatively with listing within 2 years of starting dialysis (odds ratio, 0.7; 95% confidence interval, 0.58 to 0.9). Conclusions Patient case mix accounts for most of the intercenter variation seen in access to transplantation in the United Kingdom, with practice patterns also contributing some variation. Socioeconomic inequity exists despite having a universal health care system

Deep learning optimized single-pixel LiDAR

Interest in autonomous transport has led to a demand for 3D imaging technologies capable of resolving fine details at long range. Light detection and ranging (LiDAR) systems have become a key technology in this area, with depth information typically gained through time-of-flight photon-counting measurements of a scanned laser spot. Single-pixel imaging methods offer an alternative approach to spot-scanning, which allows a choice of sampling basis. In this work, we present a prototype LiDAR system, which compressively samples the scene using a deep learning optimized sampling basis and reconstruction algorithms. We demonstrate that this approach improves scene reconstruction quality compared to an orthogonal sampling method, with reflectivity and depth accuracy improvements of 57% and 16%, respectively, for one frame per second acquisition rates. This method may pave the way for improved scan-free LiDAR systems for driverless cars and for fully optimized sampling to decision-making pipelines

Calcium/calmodulin-dependent kinase II and nitric oxide synthase 1 dependent modulation of ryanodine receptors during β-adrenergic stimulation is restricted to the dyadic cleft.

In cardiac myocytes, β‐adrenergic stimulation enhances Ca2+ cycling through an integrated signalling cascade modulating L‐type Ca2+ channels (LTCCs), phospholamban and ryanodine receptors (RyRs). Ca2+/calmodulin‐dependent kinase II (CaMKII) and nitric oxide synthase 1 (NOS1) are proposed as prime mediators for increasing RyR open probability. We investigate whether this pathway is confined to the high Ca2+ microdomain of the dyadic cleft and thus to coupled RyRs. Pig ventricular myocytes are studied under whole‐cell voltage‐clamp and confocal line‐scan imaging with Fluo‐4 as a [Ca2+]i indicator. Following conditioning depolarizing pulses, spontaneous RyR activity is recorded as Ca2+ sparks, which are assigned to coupled and non‐coupled RyR clusters. Isoproterenol (ISO) (10 nm) increases Ca2+ spark frequency in both populations of RyRs. However, CaMKII inhibition reduces spark frequency in coupled RyRs only; NOS1 inhibition mimics the effect of CaMKII inhibition. Moreover, ISO induces the repetitive activation of coupled RyR clusters through CaMKII activation. Immunostaining shows high levels of CaMKII phosphorylation at the dyadic cleft. CaMKII inhibition reduces ICaL and local Ca2+ transients during depolarizing steps but has only modest effects on amplitude or relaxation of the global Ca2+ transient. In contrast, protein kinase A (PKA) inhibition reduces spark frequency in all RyRs concurrently with a reduction of sarcoplasmic reticulum Ca2+ content, Ca2+ transient amplitude and relaxation. In conclusion, CaMKII activation during β‐adrenergic stimulation is restricted to the dyadic cleft microdomain, enhancing LTCC‐triggered local Ca2+ release as well as spontaneous diastolic Ca2+ release whilst PKA is the major pathway increasing global Ca2+ cycling. Selective CaMKII inhibition may reduce potentially arrhythmogenic release without negative inotropy

Control of rotorcraft retreating blade stall using air-jet vortex generators

A series of low-speed wind tunnel tests were carried out on an oscillating airfoil fitted with two rows of air-jet vortex generators (AJVGs). The airfoil used had an RAE 9645 section and the two spanwise arrays of AJVGs were located at x/c=0.12 and 0.62. The devices and their distribution were chosen to assess their ability to modify/control dynamic stall; the goal being to enhance the aerodynamic performance of helicopter rotors on the retreating blade side of the disc. The model was pitched about the quarter chord with a reduced frequency (k) of 0.1 in a sinusoidal motion defined by a=15o+10sin_ t. The measured data indicate that, for continuous blowing from the front row of AJVGs with a momentum blowing coefficient (C μ) greater than 0.008, modifications to the stalling process are encouraging. In particular, the pitching moment behavior exhibits delayed stall and there is a marked reduction in the normal force hysteresis

A multi-centre qualitative study exploring the experiences of UK South Asian and White Diabetic Patients referred for renal care

Background An exploration of renal complications of diabetes from the patient perspective is important for developing quality care through the diabetic renal disease care pathway. Methods Newly referred South Asian and White diabetic renal patients over 16 years were recruited from nephrology outpatient clinics in three UK centres - Luton, West London and Leicester – and their experiences of the diabetes and renal care recorded. A semi-structured qualitative interview was conducted with 48 patients. Interview transcripts were analysed thematically and comparisons made between the White and South Asian groups. Results 23 South Asian patients and 25 White patients were interviewed. Patient experience of diabetes ranged from a few months to 35 years with a mean time since diagnosis of 12.1 years and 17.1 years for the South Asian and White patients respectively. Confusion emerged as a response to referral shared by both groups. This sense of confusion was associated with reported lack of information at the time of referral, but also before referral. Language barriers exacerbated confusion for South Asian patients. Conclusions The diabetic renal patients who have been referred for specialist renal care and found the referral process confusing have poor of awareness of kidney complications of diabetes. Healthcare providers should be more aware of the ongoing information needs of long term diabetics as well as the context of any information exchange including language barriers

Hyperactive ryanodine receptors in human heart failure and ischaemic cardiomyopathy reside outside of couplons

Aims In ventricular myocytes from humans and large mammals, the transverse and axial tubular system (TATS) network is less extensive than in rodents with consequently a greater proportion of ryanodine receptors (RyRs) not coupled to this membrane system. TATS remodelling in heart failure (HF) and after myocardial infarction (MI) increases the fraction of non-coupled RyRs. Here we investigate whether this remodelling alters the activity of coupled and non-coupled RyR sub-populations through changes in local signalling. We study myocytes from patients with end-stage HF, compared with non-failing (non-HF), and myocytes from pigs with MI and reduced left ventricular (LV) function, compared with sham intervention (SHAM).Methods and resultsSingle LV myocytes for functional studies were isolated according to standard protocols. Immunofluorescent staining visualized organization of TATS and RyRs. Ca2+ was measured by confocal imaging (fluo-4 as indicator) and using whole-cell patch-clamp (37°C). Spontaneous Ca2+ release events, Ca2+ sparks, as a readout for RyR activity were recorded during a 15 s period following conditioning stimulation at 2 Hz. Sparks were assigned to cell regions categorized as coupled or non-coupled sites according to a previously developed method. Human HF myocytes had more non-coupled sites and these had more spontaneous activity than in non-HF. Hyperactivity of these non-coupled RyRs was reduced by Ca2+/calmodulin-dependent kinase II (CaMKII) inhibition. Myocytes from MI pigs had similar changes compared with SHAM controls as seen in human HF myocytes. As well as by CaMKII inhibition, in MI, the increased activity of non-coupled sites was inhibited by mitochondrial reactive oxygen species (mito-ROS) scavenging. Under adrenergic stimulation, Ca2+ waves were more frequent and originated at non-coupled sites, generating larger Na+/Ca2+ exchange currents in MI than in SHAM. Inhibition of CaMKII or mito-ROS scavenging reduced spontaneous Ca2+ waves, and improved excitation–contraction coupling.ConclusionsIn HF and after MI, RyR microdomain re-organization enhances spontaneous Ca2+ release at non-coupled sites in a manner dependent on CaMKII activation and mito-ROS production. This specific modulation generates a substrate for arrhythmia that appears to be responsive to selective pharmacologic modulation

Estimating Health-State Utility Values in Kidney Transplant Recipients and Waiting-List Patients Using the EQ-5D-5L.

OBJECTIVES: To report health-state utility values measured using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) in a large sample of patients with end-stage renal disease and to explore how these values vary in relation to patient characteristics and treatment factors. METHODS: As part of the prospective observational study entitled "Access to Transplantation and Transplant Outcome Measures," we captured information on patient characteristics and treatment factors in a cohort of incident kidney transplant recipients and a cohort of prevalent patients on the transplant waiting list in the United Kingdom. We assessed patients' health status using the EQ-5D-5L and conducted multivariable regression analyses of index scores. RESULTS: EQ-5D-5L responses were available for 512 transplant recipients and 1704 waiting-list patients. Mean index scores were higher in transplant recipients at 6 months after transplant surgery (0.83) compared with patients on the waiting list (0.77). In combined regression analyses, a primary renal diagnosis of diabetes was associated with the largest decrement in utility scores. When separate regression models were fitted to each cohort, female gender and Asian ethnicity were associated with lower utility scores among waiting-list patients but not among transplant recipients. Among waiting-list patients, longer time spent on dialysis was also associated with poorer utility scores. When comorbidities were included, the presence of mental illness resulted in a utility decrement of 0.12 in both cohorts. CONCLUSIONS: This study provides new insights into variations in health-state utility values from a single source that can be used to inform cost-effectiveness evaluations in patients with end-stage renal disease