A catalyst for transforming health systems and person-centred care: Canadian national position statement on patient-reported outcomes.

Background: Patient-reported outcomes (pros) are essential to capture the patient's perspective and to influence care. Although pros and pro measures are known to have many important benefits, they are not consistently being used and there is there no Canadian pros oversight. The Position Statement presented here is the first step toward supporting the implementation of pros in the Canadian health care setting. Methods: The Canadian pros National Steering Committee drafted position statements, which were submitted for stakeholder feedback before, during, and after the first National Canadian Patient Reported Outcomes (canpros) scientific conference, 14-15 November 2019 in Calgary, Alberta. In addition to the stakeholder feedback cycle, a patient advocate group submitted a section to capture the patient voice. Results: The canpros Position Statement is an outcome of the 2019 canpros scientific conference, with an oncology focus. The Position Statement is categorized into 6 sections covering 4 theme areas: Patient and Families, Health Policy, Clinical Implementation, and Research. The patient voice perfectly mirrors the recommendations that the experts reached by consensus and provides an overriding impetus for the use of pros in health care. Conclusions: Although our vision of pros transforming the health care system to be more patient-centred is still aspirational, the Position Statement presented here takes a first step toward providing recommendations in key areas to align Canadian efforts. The Position Statement is directed toward a health policy audience; future iterations will target other audiences, including researchers, clinicians, and patients. Our intent is that future versions will broaden the focus to include chronic diseases beyond cancer.

WE-G-217A-07: Increased MR Spatial Accuracy with Improved Gradient Nonlinearity and Magnet Inhomogeneity Correction.

PURPOSE: To develop improved distortion correction of MR images based on higher degree spherical harmonic models of the gradient system and the main magnetic field. METHODS: The induced field gradient along all three axes can be modeled by first order spherical harmonics. These models provide a true encoding of the physical location of a spin to the frequency at which it is detected. Currently on many commercial systems, only the lower 5 degrees of the model are used for gradient nonlinearity correction. While this provides sufficient accuracy for diagnostic imaging, the gradient nonlinearity correction was extended to include all first order harmonics up to the 9th degree to improve the spatial accuracy of the images. Using zeroth degree spherical harmonics up to the 20th order, a model of the main magnetic field was also incorporated into the correction algorithm. Shifts caused by field inhomogeneity were calculated using knowledge of the receiver bandwidth, frequency encode direction, and the magnetic field at any given point. These corrections were applied to images of a 50 cm diameter phantom, acquired with an extended FOV 3D FGRE sequence. Any improvements in spatial accuracy were measured in the resulting images. RESULTS: Visual improvements in spatial accuracy were observed with both corrections. With standard gradient nonlinearity correction, edges of the phantom were distorted in a wave-like fashion. With accurate models, almost all of the errors at the edges of the phantom were corrected when both gradient and field homogeneity corrections were applied. CONCLUSION: With accurate models of the gradient and magnetic field, the two greatest system-induced spatial errors can be corrected. This improved spatial accuracy enables the use of widebore MR scanners for therapy planning on large FOV images and guidance of percutaneous devices. Further applications include extended FOV imaging for combined PET-MR systems. All authors are employed by General Electric Healthcare.

WE-G-217A-06: Spatial Accuracy Quantification of an MR System.

PURPOSE: To develop a phantom and measurement protocol for quantifying spatial accuracy of an MR imaging system over its entire imaging volume. METHODS: The measurement protocol is comprised of a phantom, a set of MR sequence parameters for imaging the phantom, and analysis software for calculating spatial errors in the acquired phantom images. The phantom covers the entire imaging volume of the scanner above the patient table. It consists of layers of tooling foam which does not produce any detectable signal on conventional MR images, embedded with a matrix of oil capsules to serve as markers. To account for possible spatial errors in the construction of the phantom, the phantom was imaged with CT to create a gold standard data set. On MR scanners, the phantom is acquired with a 3D FGRE sequence that covers an extended FOV of 61.44 mm and with bandwidth = ±62.5 kHz. Error measurements are performed by detecting markers in the image sets and identifying them based on their known locations on the phantom. The spatial error of a marker is defined as the difference between its locations on the MR and CT image sets. RESULTS: The phantom was constructed and the measurement protocol was executed on two different MR scanners. Some markers were located in areas of severe field inhomogeneity or gradient nonlinearity, and could not be adequately detected for analysis. Maximum errors over concentric spherical regions were observed by plotting the error of each marker as a function of their distance from isocenter. CONCLUSION: The proposed phantom and protocol can be an effective tool for verifying the spatial accuracy of an MR system, which in turn can improve the accuracy and confidence of MR guided therapies. Data from this protocol may also be used in the development of advanced distortion correction algorithms. Employed by General Electric Healthcare.

Realignment capability of the nCPMG sequence.

The nCPMG sequence is based on a particular phase modulation of the refocusing pulse train, and was originally designed for rendering the spin echo amplitude insensitive to the initial magnetization phase. This pulse sequence has the peculiarity of being easily invertible, which enables perfect driven equilibrium experiments, in the absence of relaxation. This magnetization 'realignment' is effective for all three components. Hence the overall operation is transparent. Supporting theory is presented here, together with the first direct experimental proof of the claim. The experiment shows that, with the present stabilization sequence, perfect realignment is indeed made possible for a range of refocusing pulse nutation angles from 130° to 230°.

Imaging near metal with a MAVRIC-SEMAC hybrid.

The recently developed multi-acquisition with variable resonance image combination (MAVRIC) and slice-encoding metal artifact correction (SEMAC) techniques can significantly reduce image artifacts commonly encountered near embedded metal hardware. These artifact reductions are enabled by applying alternative spectral and spatial-encoding schemes to conventional spin-echo imaging techniques. Here, the MAVRIC and SEMAC concepts are connected and discussed. The development of a hybrid technique that utilizes strengths of both methods is then introduced. The presented technique is shown capable of producing minimal artifact, high-resolution images near total joint replacements in a clinical setting.

Chloroplast evidence for geographic stasis of the Australian bird-dispersed shrub Tasmannia lanceolata (Winteraceae).

Few chloroplast-based genetic studies have been undertaken for plants of mesic temperate forests in the southern hemisphere and fossil-based models have provided evidence of vegetation history only at the broadest scales in this region. This study investigates the chloroplast DNA phylogeography of Tasmannia lanceolata (Winteraceae), a fleshy-fruited, bird-dispersed shrub that is widespread in the mountains of southeastern Australia and Tasmania. Thirty haplotypes were identified after sequencing 3206 bp of chloroplast DNA in each of 244 individuals collected across the species' range. These haplotypes showed unexpectedly strong phylogeographic structuring, including a phylogeographic break within a continuous part of the species' range, with the distribution of four major clades mostly not overlapping, and geographic structuring of haplotypes within these clades. This strong geographic patterning of chloroplast DNA provided evidence for the survival of T. lanceolata in multiple putative wet forest refugia as well as evidence for additional wet forest species refugia in southeastern Australia. In western Tasmania lower haplotype diversity below the LGM tree line compared to above the LGM tree line suggests that glacial refugia at high altitudes may have been important for T. lanceolata. The level of geographic structuring in T. lanceolata is similar to gravity dispersed southern hemisphere plants such as Nothofagus and Eucalyptus. Behavioural traits of the birds transporting seed may have had a strong bearing on the limited transport of T. lanceolata seed, although factors limiting establishment, possibly including selection, may also have been important.

Recurrent nuclear DNA introgression accompanies chloroplast DNA exchange between two eucalypt species.

Numerous studies within plant genera have found geographically structured sharing of chloroplast (cp) DNA among sympatric species, consistent with introgressive hybridization. Current research is aimed at understanding the extent, direction and significance of nuclear (nr) DNA exchange that accompanies putative cpDNA exchange. Eucalyptus is a complex tree genus for which cpDNA sharing has been established between multiple species. Prior phylogeographic analysis has indicated cpDNA introgression into the widespread forest species Eucalyptus globulus from its rare congener E. cordata. In this study, we use AFLP markers to characterize corresponding nrDNA introgression, on both a broad and fine spatial scale. Using 388 samples we examine (i) the fine-scale spatial structure of cp and nrDNA introgression from E. cordata into E. globulus at a site in natural forest and (ii) broad-scale patterns of AFLP marker introgression at six additional mixed populations. We show that while E. globulus and E. cordata retain strongly differentiated nuclear gene pools overall, leakage of nrDNA occurs at mixed populations, with some AFLP markers being transferred to E. globulus recurrently at different sites. On the fine scale, different AFLP fragments show varying distances of introgression into E. globulus, while introgression of cpDNA is extensive. The frequency of E. cordata markers in E. globulus is correlated with spatial proximity to E. cordata, but departs from expectations based on AFLP marker frequency in E. cordata, indicating that selection may be governing the persistence of introgressed fragments in E. globulus.

Time-domain control of ultrahigh-frequency nanomechanical systems.

Nanoelectromechanical systems could have applications in fields as diverse as ultrasensitive mass detection and mechanical computation, and can also be used to explore fundamental phenomena such as quantized heat conductance and quantum-limited displacement. Most nanomechanical studies to date have been performed in the frequency domain. However, applications in computation and information storage will require transient excitation and high-speed time-domain operation of nanomechanical systems. Here we show a time-resolved optical approach to the transduction of ultrahigh-frequency nanoelectromechanical systems, and demonstrate that coherent control of nanomechanical oscillation is possible through appropriate pulse programming. A series of cantilevers with resonant frequencies ranging from less than 10 MHz to over 1 GHz are characterized using the same pulse parameters.

Prevalence of hypogonadism in male patients with renal failure.

BACKGROUND: Hypogonadism in men may be secondary to renal failure and is well recognised in patients with end-stage renal disease. It is thought to contribute to the sexual dysfunction and osteoporosis experienced by these patients. However, the association between hypogonadism and lesser degrees of renal dysfunction is not well characterised. METHODS: The gonadal status of 214 male patients (mean age 56 (SD 18) years) attending a renal centre was studied; 62 of them were receiving haemodialysis and 22 continuous ambulatory peritoneal dialysis for end-stage renal disease, whereas 34 patients had functioning renal transplants and 96 patients were in the low-clearance phase. Non-fasting plasma was analysed for testosterone, follicle-stimulating hormone, luteinising hormone, sex hormone-binding globulin, parathyroid hormone and haemoglobin. Creatinine clearance was estimated in patients not on dialysis, and Kt/V and urea reduction ratio were assessed in patients on dialysis. Testosterone concentrations were classified as normal (>14 nmol/l), low-normal (10-14 nmol/l) or low (<10 nmol/l). RESULTS: 56 (26.2%) patients had significantly low testosterone levels and another 65 (30.3%) had low-normal levels. No significant changes were seen in sex hormone-binding globulin or gonadotrophin levels. Gonadal status was not correlated with haemoglobin level, parathyroid hormone level, creatinine clearance, or dialysis duration or adequacy. CONCLUSION: Over half of patients with renal failure, even in the pre-dialysis phase, have low or low-normal levels of testosterone, which may be a potentially reversible risk factor for osteoporosis and sexual dysfunction. These patients may be candidates for testosterone-replacement therapy, which has been shown to improve bone mineral-density and libido in men with low and low-normal testosterone levels.

Maternal inheritance of mitochondria in Eucalyptus globulus.

It is important to verify mitochondrial inheritance in plant species in which mitochondrial DNA (mtDNA) will be used as a source of molecular markers. We used a polymerase chain reaction (PCR)/restriction fragment length polymorphism (RFLP) approach to amplify mitochondrial introns from subunits 1, 4, 5, and 7 of NADH dehydrogenase (nad) and cytochrome oxidase subunit II (cox2) in Eucalyptus globulus. PCR fragments were then either sequenced or cut with restriction enzymes to reveal polymorphism. Sequencing cox2 showed that eucalypts lack the intron between exons 1 and 2. One polymorphism was found in intron 2-3 of nad7 following restriction digests with HphI. Fifty-four F1 progeny from seven families with parents distinguishable in their mitochondrial nad7 were screened to show that mitochondria were maternally inherited in E. globulus. These results constitute the first report of mitochondrial inheritance in the family Myrtaceae.

Menstrual cycle variation of apparent diffusion coefficients measured in the normal breast using MRI.

Recent investigations have shown that tumors may be distinguished from benign lesions in the breast based on differences in apparent diffusion coefficient (ADC) values. The goal of this study was to assess the magnitude of normal variations in the measured ADC of breast parenchyma during the menstrual cycle. Eight healthy female subjects were scanned once a week for 4 weeks, using a diffusion-weighted single-shot fast spin-echo (DW-SSFSE) sequence. The ADC of breast fibroglandular tissue was calculated for each woman at each time point. Results showed a trend of decreased ADC during the second week of the cycle, and increased ADC during the final week. However, no significant influence of menstrual cycle on breast ADC values was identified. The results of this study show that the normal fluctuation of breast ADC is relatively small, and the coefficient of variation was determined to be 5.5% for our group of volunteers during a menstrual cycle. Nonetheless, breast diffusion measurements for tumor differentiation and evaluation of treatment response should be interpreted with consideration of normal variability.

Cystadenomas of the liver: a spectrum of disease.

OBJECTIVES: To describe the wide variation in presentation of cystadenomas of the liver and to delineate useful tests for diagnosis and effective surgical treatment. DESIGN: A case series. SETTING: A university-affiliated hospital. PATIENTS: Four patients (3 women, 1 man) having cystadenoma of the liver, 2 of whom had associated mesenchymal stroma. MAIN OUTCOME MEASURES: Serum and cyst fluid carcinoembryonic antigen (CEA) and CA19-9 levels, type of surgery, morbidity and recurrence rates. RESULTS: Cyst fluid CEA and CA19-9 levels were elevated. One patient had resection, 2 had complete enucleation and 1 had partial enucleation. There were no deaths. Morbidity included 1 wound infection; there were no biliary fistulas. The patient with partial enucleation had a radiologically confirmed recurrence. CONCLUSIONS: Analysis of cyst fluid CEA and CA19-9 is useful for diagnosis; besides hepatic resection, complete enucleation should be considered as a reasonable treatment for patients with this disease.

Chloroplast sharing in the Tasmanian eucalypts.

The biogeographic pattern of chloroplast DNA (cpDNA) haplotypes in Eucalyptus on the island of Tasmania is consistent with reticulate evolution, involving at least 12 Tasmanian species from the subgenus Symphyomyrtus. Intraspecific cpDNA polymorphism in 14 of 17 species is coupled with extensive sharing of identical haplotypes across populations of different species in the same geographic area. Haplotype diversity is lowest in central regions of Tasmania formerly occupied by alpine vegetation during glacial intervals and in northern regions that were periodically linked to continental Australia by land bridges. The observed distribution of several cpDNA haplotypes unique to Tasmania coincides with modeled locations of glacial refugia in coastal areas of Tasmania and shows the power of cpDNA in unraveling the complex history of past distributions of Eucalyptus. The results suggest that the model of evolution of the eucalypts should be reassessed to allow for the anastomosing effects of interspecific hybridization and introgression.

Cystadenoma of the liver without mesenchymal stroma in a female following hormonal therapy for acne.

BACKGROUND: Liver cystadenomas are relatively rare tumours that can be difficult to diagnose; treatment entails complete surgical extirpation either by either anatomical resection or enucleation. CASE OUTLINE: A 19-year-old woman presented with acute onset of abdominal pain and was found to have a multilocular giant liver cyst.The cyst was percutaneously drained; CEA and CA 19-9 tumour markers were elevated in this cyst fluid: CEA 96 microg/L, CAI9-9 37 550 kU/L. The cyst was completely enucleated and has not recurred. Pathological examination confirmed a cystadenoma without mesenchymal stroma, and tumour oestrogen and progesterone receptors were negative. DISCUSSION: This is the fourth report of a liver cystadenoma without mesenchymal stroma in a female and the first to document elevated cyst fluid tumour markers. This case also illustrates the possible relationship between hormonal therapy and tumour growth.

A multireflection cell for enhanced absorbance detection in microchip-based capillary electrophoresis devices.

The design, fabrication and testing of a photolithographically fabricated, glass-based multireflection absorbance cell for microfluidic devices, in particular microchip-based capillary electrophoresis (CE) systems is described. A multireflection cell was fabricated lithographically using a three-mask process to pattern aluminum mirrors above and below a flow channel in a chip, with 30 microm diameter optical entrance or exit apertures (one in each mirror) positioned 200 microm apart. Source and detector were positioned on opposite sides, and the metal mirrors were made 1 cm square, to reduce stray light effects. Calibration curves using bromothymol blue (BTB) with a 633 nm source (He:Ne laser) were linear to at least 0.5 absorbance units, with typical r2 values of 0.9997, relative standard deviations in the slopes of +/- 1.3%, and intercepts of zero within experimental error. Effective optical pathlengths of 50-272 microm were achieved, compared to single-pass pathlengths of 10-30 microm, corresponding to sensitivity enhancements (i.e., optical path length increase) of 5 to 10-fold over single-pass devices. Baseline absorbance noise varied within a factor of two in almost all devices, depending only weakly on path length. This device can give much higher absorbance sensitivity, and should be much easier to manufacture than planar, glass-based devices previously reported.

Magnetic resonance imaging of benign spinal lesions simulating metastasis: role of diffusion-weighted imaging.

In an attempt to avoid unnecessary therapy, this article demonstrates benign vertebral body lesions that mimic metastatic disease in cancer patients with back pain. The magnetic resonance imaging features that aid in differential diagnosis are demonstrated. In addition, the value of diffusion-weighted spinal imaging to further aid in distinguishing benign from malignant disease is described.

A fast 3D look-locker method for volumetric T1 mapping.

We introduce a fast technique, based on the principles of the 2D Look-Locker T1 measurement scheme, to rapidly acquire the data for accurate maps of T1 in three dimensions. The acquisition time has been shortened considerably by segmenting the acquisition of the k(y) phase encode lines. Using this technique, the data for a 256 x 128 x 32 volumetric T1 measurement can be acquired in 7.6 min. T1 measurements made in phantoms with T1s between 200 and 1200 ms had an accuracy of 4% and a reproducibility of 3.5%. Measurements of T1 made in normal brain using the fast 3D sequence corresponded well with inversion-recovery fast spin-echo measurements.

Incongruence between chloroplast and species phylogenies in Eucalyptus subgenus Monocalyptus (Myrtaceae).

Seventy-eight polymorphic cpDNA (chloroplast DNA) characters were found in 13 closely related taxa from Eucalyptus series Amygdalinae (subgenus Monocalyptus) and seven potential outgroup taxa. The strict consensus of six cladograms generated from cpDNA data confirmed monophyly of Monocalyptus. However, cpDNA phylogeny within Monocalyptus was incongruent with taxonomic classification, being more related to geography, even when accessions were from divergent series. Monocalyptus cpDNA formed two major clades. On the island of Tasmania cpDNA was restricted to a single clade, exhibited very little variation, and was phylogenetically related to cpDNA found in central and western Victoria. In contrast, cpDNA of mainland monocalypt taxa was more variable, even within the Amygdalinae. Four out of six Tasmanian Amygdalinae species were polymorphic. The difference between cpDNA of replicates was often greater than differences between species from different series. The low level of cpDNA variation and extensive morphological intergradation between the Tasmanian endemics suggest recent speciation. However, the transfer of cpDNA through hybridization between lineages is the most likely explanation for the observed sharing of cpDNA across series. This study highlights that the geographical pattern to cpDNA variation in Eucalyptus may be an important source of information on past plant distributions in Australia.

ITS sequence data resolve higher level relationships among the eucalypts.

Sequences of the internal transcribed spacer (ITS) region of the nuclear ribosomal DNA were obtained for 35 species of Eucalyptus s.s. and seven taxa representing five outgroup genera (Allosyncarpia, Angophora, Arillastrum, Corymbia, and Stockwellia). The sequences were analyzed cladistically. The data distinguished clearly between the two major subgenera of Eucalyptus s.s. (Symphyomyrtus and Monocalyptus) but indicated that subgenus Eudesmia may be paraphyletic. ITS sequence data demonstrated the potential to resolve relationships between sections within subgenus Symphyomyrtus. Within sections, however, taxa were poorly differentiated. At the generic level, Corymbia appeared to be paraphyletic due to the exclusion of Angophora. The positions of Allosyncarpia and Arillastrum relative to the ingroup remain unresolved. ITS sequence data may prove valuable for resolving other phylogenetic relationships at higher taxonomic levels within Eucalyptus.