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Premise: The Caryophyllaceae (the carnation family) have undergone multiple transitions into colder climates and convergence on cushion plant adaptation, indicating that they may provide a natural system for cold adaptation research. Previous research has suggested that putative ancient whole-genome duplications (WGDs) are correlated with niche shifts into colder climates across the Caryophyllales. Here, we explored the genomic changes potentially involved in one of these discovered shifts in the Caryophyllaceae., Methods: We constructed a data set combining 26 newly generated transcriptomes with 45 published transcriptomes, including 11 cushion plant species across seven genera. With this data set, we inferred a dated phylogeny for the Caryophyllaceae and mapped ancient WGDs and gene duplications onto the phylogeny. We also examined functional groups enriched for gene duplications related to the climatic shift., Results: The ASTRAL topology was mostly congruent with the current consensus of relationships within the family. We inferred 15 putative ancient WGDs in the family, including eight that have not been previously published. The oldest ancient WGD (ca. 64.4-56.7 million years ago), WGD1, was found to be associated with a shift into colder climates by previous research. Gene regions associated with ubiquitination were overrepresented in gene duplications retained after WGD1 and those convergently retained by cushion plants in Colobanthus and Eremogone, along with other functional annotations., Conclusions: Gene family expansions induced by ancient WGDs may have contributed to the shifts to cold climatic niches in the Caryophyllaceae. Transcriptomic data are crucial resources that help unravel heterogeneity in deep-time evolutionary patterns in plants., (© 2024 The Author(s). American Journal of Botany published by Wiley Periodicals LLC on behalf of Botanical Society of America.)

Background and Purpose: Conclusions from prior literature regarding the impact of sex, age, and height on spinal cord (SC) MRI morphometrics are conflicting, while the effect of body weight on SC morphometrics has been found to be nonsignificant. The purpose of this case-control study is to assess the associations between cervical SC MRI morphometric parameters and age, sex, height, and weight to establish their potential role as confounding variables in a clinical study of people with multiple sclerosis (MS) compared to a cohort of healthy volunteers., Methods: Sixty-nine healthy volunteers and 31 people with MS underwent cervical SC MRI at 3 Tesla field strength. Images were centered at the C3/C4 intervertebral disc and processed using Spinal Cord Toolbox v.4.0.2. Mixed-effects linear regression models were used to evaluate the effects of biological variables and disease status on morphometric parameters., Results: Sex, age, and height had significant effects on cord and gray matter (GM) cross-sectional area (CSA) as well as the GM:cord CSA ratio. There were no significant effects of body weight on morphometric parameters. The effect of MS disease duration on cord CSA in the C4 level was significant when controlling for all other variables., Conclusions: Studies of disease-related changes in SC morphometry should control for sex, age, and height to account for physiological variation., (© 2024 The Author(s). Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Background: Based on a high incidence of genomic alteration in the cell cycle and DNA damage and response (DDR)-related pathways in small cell lung cancer (SCLC), the clinical efficacy of the DDR-targeting agent olaparib (PARP inhibitor) as monotherapy and in combination with ceralasertib (ATR inhibitor) in relapsed or refractory SCLC was evaluated., Methods: As part of a phase 2 biomarker driven umbrella study, patients with SCLC and predefined DDR gene alterations who failed to benefit from prior platinum-based regimens were allocated to the olaparib monotherapy arm and nonbiomarker-selected patients were allocated to the olaparib and ceralasertib combination arm., Results: In the olaparib monotherapy arm (n = 15), the objective response rate was 6.7% (one partial response), and the disease control rate was 33.3%, including three patients with stable disease. The median progression-free survival was 1.3 months (95% CI, 1.2-NA). In the combination arm (n = 26), the objective response rate and disease control rate were 3.8% and 42.3%, respectively, with one partial response and 10 patients with stable disease. The median progression-free survival was 2.8 months (95% CI, 1.8-5.4). Treatment was generally well tolerated except for one fatal case of neutropenic fever in the combination arm., Conclusions: Targeting DDR pathways with olaparib as a single agent or in combination with ceralasertib did not meet the predefined efficacy end point. However, disease stabilization was more evident in the combination arm. Further investigation of the combination of olaparib in SCLC should be performed with diverse combinations and patient selection strategies to maximize efficacy., (© 2023 American Cancer Society.)

Background and Purpose: Paramagnetic rims and the central vein sign (CVS) are proposed imaging markers of multiple sclerosis (MS) lesions. Using 7 tesla magnetic resonance imaging, we aimed to: (1) characterize the appearance of paramagnetic rim lesions (PRLs); (2) assess whether PRLs and the CVS are associated with higher levels of MS pathology; and (3) compare the characteristics between subjects with and without PRLs in early MS., Methods: Prospective study of 32 treatment-naïve subjects around the time of diagnosis who were assessed for the presence of PRLs and the CVS. Comparisons of lesion volume and macromolecular pool size ratio (PSR) index, a proxy of myelin integrity, between PRLs and non-PRLs, and CVS-positive and CVS-negative lesions were carried out. Differences in clinical/demographic characteristics between patients with PRLs and those without were tested., Results: Fifteen subjects had ≥1 PRL for a total of 36 PRLs, of which two-thirds had a full rim. PRLs predicted a larger lesion size and decreased PSR signal. Lesion volume and presence of cervical spine lesions were significantly different between subjects with PRLs and those without, although neither remained significant after adjusting for multiple comparisons. One hundred and eighty-one lesions with CVS were identified with no differences between CVS-positive and CVS-negative lesions in volume (p = .27) and PSR values (p = .62)., Conclusions: PRLs, but not CVS-positive lesions, are larger and have lower myelin integrity. Our findings indicate that PRLs are associated with higher levels of lesion-specific pathology prior to the start of disease-modifying therapy., (© 2023 American Society of Neuroimaging.)

Background: Intramuscular injections of hypertonic saline are commonly used to induce experimental muscle pain, but reliability data on this technique are lacking. This study investigated the intra- and interindividual reliability of pain measures from a hypertonic saline injection into the vastus lateralis., Methods: Fourteen healthy participants (6 female) attended three laboratory visits where they received an intramuscular injection of 1 mL hypertonic saline into the vastus lateralis. Changes in pain intensity were recorded on an electronic visual analogue scale, and pain quality was assessed after pain had resolved. Reliability was assessed with the coefficient of variation (CV), minimum detectable change (MDC) and intraclass correlation coefficient (ICC) with 95% CIs., Results: Mean pain intensity displayed high levels of intraindividual variability (CV = 16.3 [10.5-22.0]%) and 'poor' to 'very good' relative reliability (ICC = 0.71 [0.45-0.88]) but had a MDC of 11 [8-16] au (out of 100). Peak pain intensity exhibited high levels of intraindividual variability (CV = 14.8 [8.8-20.8]%) with 'moderate' to 'excellent' levels of relative reliability (ICC = 0.81 [0.62-0.92]), whereas the MDC was 18 [14-26] au. Measures of pain quality exhibited good reliability. Interindividual variability in pain measures was high (CV > 37%)., Conclusions: Intramuscular injections of 1 mL of hypertonic saline into the vastus lateralis display substantial levels of interindividual variability, but MDC is below the clinically important changes in pain. This model of experimental pain is suitable for studies involving repeated exposures., Significance: Many pain research studies have performed intramuscular injections of hypertonic saline to investigate responses to muscle pain. However, the reliability of this technique is not well established. We examined the pain response over three repeated sessions of a hypertonic saline injection. The pain induced by hypertonic saline has considerable interindividual variability but has largely acceptable intraindividual reliability. Therefore, the injections of hypertonic saline to induce muscle pain are a reliable model of experimental muscle pain., (© 2023 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

Purpose: The need to detect and quantify brain lactate accurately by MRS has stimulated the development of editing sequences based on J coupling effects. In J-difference editing of lactate, threonine can be co-edited and it contaminates lactate estimates due to the spectral proximity of the coupling partners of their methyl protons. We therefore implemented narrow-band editing 180° pulses (E180) in MEGA-PRESS acquisitions to resolve separately the 1.3-ppm resonances of lactate and threonine., Methods: Two 45.3-ms rectangular E180 pulses, which had negligible effects 0.15-ppm away from the carrier frequency, were implemented in a MEGA-PRESS sequence with TE 139 ms. Three acquisitions were designed to selectively edit lactate and threonine, in which the E180 pulses were tuned to 4.1 ppm, 4.25 ppm, and a frequency far off resonance. Editing performance was validated with numerical analyses and acquisitions from phantoms. The narrow-band E180 MEGA and another MEGA-PRESS sequence with broad-band E180 pulses were evaluated in six healthy subjects., Results: The 45.3-ms E180 MEGA offered a difference-edited lactate signal with lower intensity and reduced contamination from threonine compared to the broad-band E180 MEGA. The 45.3 ms E180 pulse had MEGA editing effects over a frequency range larger than seen in the singlet-resonance inversion profile. Lactate and threonine in healthy brain were both estimated to be 0.4 ± 0.1 mM, with reference to N-acetylaspartate at 12 mM., Conclusion: Narrow-band E180 MEGA editing minimizes threonine contamination of lactate spectra and may improve the ability to detect modest changes in lactate levels., (© 2023 International Society for Magnetic Resonance in Medicine.)

Objective: Carnobacterium maltaromaticum is considered an emerging pathogen of salmonids in the United States and around the world., Methods: Bacterial cultures obtained from the posterior kidney and skin of moribund Rainbow Trout Oncorhynchus mykiss from a commercial aquaculture facility in Virginia, USA, grew C. maltaromaticum, which was confirmed by additional phenotypic and molecular characterization., Result: A presumptive diagnosis based on the clinical signs, necropsy observations, histopathology, and bacterial cultures was bacterial septicemia due to C. maltaromaticum., Conclusion: This represents the first documentation of C. maltaromaticum in Rainbow Trout from Virginia., (© 2023 The Authors. Journal of Aquatic Animal Health published by Wiley Periodicals LLC on behalf of American Fisheries Society.)

Amide proton transfer-weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different institutes, and there are no agreed-on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi-center trials in larger patient cohorts and, ultimately, routine clinical use., (© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

The aim of this study was to understand COVID-19 vaccine perceptions and decision-making among a racially/ethnically diverse population of pregnant and lactating women in the Midwest. Pregnant female participants (N = 27) at least 18 years. or older living in the Midwest were recruited to participate in a maternal voices survey. A mix-methods approach was used to capture the perceptions of maternal voices concerning the COVID-19 vaccine. Participants completed an online survey on COVID-19 disease burden, vaccine knowledge, and readiness for uptake. A total of 27 participants completed the Birth Equity Network Maternal Voices survey. Most participants were African American (64%). Sixty-three percent intend to get the vaccine. Only 25% felt at-risk for contracting COVID-19, and 74% plan to consult their provider about getting the COVID-19 vaccine. At least 66% had some concerns about the safety of the vaccine. Participants indicated a willingness to receive the COVID-19 vaccine, especially if recommended by their provider. We found little racial/ethnic differences in perceptions of COVID-19 and low vaccine hesitancy., (© 2022 Wiley Periodicals LLC.)

Background and Purpose: Axonal injury is a key player of disability in persons with multiple sclerosis (pwMS). Yet, detecting and measuring it in vivo is challenging. The neurite orientation dispersion and density imaging (NODDI) proposes a novel framework for probing axonal integrity in vivo. NODDI at 3.0 Tesla was used to quantify tissue damage in pwMS and its relationship with disease progression., Methods: Eighteen pwMS (4 clinically isolated syndrome, 11 relapsing remitting, and 3 secondary progressive MS) and nine age- and sex-matched healthy controls underwent a brain MRI, inclusive of clinical sequences and a multi-shell diffusion acquisition. Parametric maps of axial diffusivity (AD), neurite density index (ndi), apparent isotropic volume fraction (ivf), and orientation dispersion index (odi) were fitted. Anatomically matched regions of interest were used to quantify AD and NODDI-derived metrics and to assess the relations between these measures and those of disease progression., Results: AD, ndi, ivf, and odi significantly differed between chronic black holes (cBHs) and T2-lesions, and between the latter and normal appearing white matter (NAWM). All metrics except ivf significantly differed between NAWM located next to a cBH and that situated contra-laterally. Only NAWM odi was significantly associated with T2-lesion volume, the timed 25-foot walk test and disease duration., Conclusions: NODDI is sensitive to tissue injury but its relationship with clinical progression remains limited., (© 2021 American Society of Neuroimaging.)

Purpose: To demonstrate the feasibility of 3D multi-shot magnetic resonance imaging acquisitions for stimulus-evoked blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in the human spinal cord in vivo., Methods: Two fMRI studies were performed at 3T. The first study was a hypercapnic gas challenge where data were acquired from healthy volunteers using a multi-shot 3D fast field echo (FFE) sequence as well as single-shot multi-slice echo-planar imaging (EPI). In the second study, another cohort of healthy volunteers performed an upper extremity motor task while fMRI data were acquired using a 3D multi-shot acquisition., Results: Both 2D-EPI and 3D-FFE were shown to be sensitive to BOLD signal changes in the cervical spinal cord, and had comparable contrast-to-noise ratios in gray matter. FFE exhibited much less signal drop-out and weaker geometric distortions compared to EPI. In the motor paradigm study, the mean number of active voxels was highest in the ventral gray matter horns ipsilateral to the side of the task and at the spinal level associated with innervation of finger extensors., Conclusions: Highly multi-shot acquisition sequences such as 3D-FFE are well suited for stimulus-evoked spinal cord BOLD fMRI., (© 2020 International Society for Magnetic Resonance in Medicine.)

Objective: To delineate the impact of treatment exposures and chronic health conditions on psychological, educational, and social outcomes in adolescent survivors of Wilms tumor., Methods: Parent reports from the Childhood Cancer Survivor Study were analyzed for 666 adolescent survivors of Wilms tumor and 698 adolescent siblings. Adjusting for race and household income, survivors were compared to siblings on the Behavior Problems Index and educational outcomes. Multivariable modified Poisson regression estimated relative risks (RR) for therapeutic exposures and chronic health conditions (CTCAE 4.03 graded) among survivors, adjusting for sex, race, income, and age at diagnosis., Results: Compared to siblings, adolescent survivors of Wilms tumor were more likely to take psychoactive medication (9.4% vs. 5.1%, p < 0.001) and utilize special education services (25.5% vs. 12.6%, p < 0.001) but did not differ significantly in emotional and behavioral problems. Survivors were less likely to be friendless (7.2% vs. 10.1%, p = 0.04) but were more likely to have difficulty getting along with friends (14.5% vs. 7.8%, p < 0.001). Among survivors, use of special education services was associated with abdomen plus chest radiation (RR = 1.98, CI:1.18-3.34). Those with grade 2-4 cardiovascular conditions had higher risk for anxiety/depression (RR = 1.95, CI:1.19-3.19), headstrong behaviors (RR = 1.91, CI:1.26-2.89), and inattention (RR = 1.56, CI:1.02-2.40)., Conclusions: Adolescent survivors of Wilms tumor were similar to siblings with respect to mental health concerns overall but were more likely to require special education. Monitoring of psychosocial and academic problems through adolescence is warranted, especially among those treated with radiation to the abdomen plus chest or with cardiac conditions., (© 2020 John Wiley & Sons Ltd.)

Background: A high percentage of small cell lung cancer (SCLC) cases harbor cell cycle-related gene mutations and RICTOR amplification. Based on underlying somatic mutations, the authors have conducted a phase 2 biomarker-driven, multiarm umbrella study., Methods: The SCLC Umbrella Korea StudiES (SUKSES) is an adaptive platform trial that undergoes continual modification according to the observed outcomes. This study included 286 patients with SCLC who failed platinum therapy and who had known genomic profiles based on a predesigned screening trial. Patients with MYC amplification or CDKN2A and TP53 co-alterations were allocated to adavosertib (SUKSES protocol C [SUKSES-C]; 7 patients) and those with RICTOR amplification were allocated to vistusertib (SUKSES-D; 4 patients). Alternatively, patients who were without any predefined biomarkers were assigned to a non-biomarker-selected arm: adavosertib (SUKSES-N1; 21 patients) or AZD2811NP (SUKSES-N3; 15 patients)., Results: Patients in the SUKSES-C and SUKSES-N1 arms demonstrated no objective response. Three patients presented with stable disease (SD) in SUKSES-C and 6 patients in SUKSES-N1. The median progression-free survival (PFS) was 1.3 months (95% confidence interval, 0.9 months to not available) for SUKSES-C and 1.2 months (95% CI, 1.1-1.4 months) for SUKSES-N1. Patients in the SUKSES-D arm demonstrated no objective response and no SD, with a PFS of 1.2 months (95% CI, 1.0 months to not available). The SUKSES-N3 arm had 5 patients with SD and a PFS of 1.6 months (95% CI, 0.9-1.7 months), without an objective response. Grade≥3 adverse events (graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.03]) were observed as follows: 3.2% in the SUKSES-C and SUKSES-N1 arms and 50.0% in the SUKSES-D arm. Target-related neutropenia (grade≥3) was observed in approximately 60.0% of patients in the AZD2811NP arm using the current dosing schedule., Conclusions: To the best of the authors' knowledge, the current study is the first biomarker-driven umbrella study conducted in patients with recurrent SCLC. Although the current study demonstrated the limited clinical efficacy of monotherapy, novel biomarker approaches using other cell cycle inhibitor(s) or combinations warrant further investigation., (© 2020 American Cancer Society.)

Purpose: Chemical exchange saturation transfer (CEST) is an MRI technique sensitive to the presence of low-concentration solute protons exchanging with water. However, magnetization transfer (MT) effects also arise when large semisolid molecules interact with water, which biases CEST parameter estimates if quantitative models do not account for macromolecular effects. This study establishes under what conditions this bias is significant and demonstrates how using an appropriate model provides more accurate quantitative CEST measurements., Methods: CEST and MT data were acquired in phantoms containing bovine serum albumin and agarose. Several quantitative CEST and MT models were used with the phantom data to demonstrate how underfitting can influence estimates of the CEST effect. CEST and MT data were acquired in healthy volunteers, and a two-pool model was fit in vivo and in vitro, whereas removing increasing amounts of CEST data to show biases in the CEST analysis also corrupts MT parameter estimates., Results: When all significant CEST/MT effects were included, the derived parameter estimates for each CEST/MT pool significantly correlated (P < .05) with bovine serum albumin/agarose concentration; minimal or negative correlations were found with underfitted data. Additionally, a bootstrap analysis demonstrated that significant biases occur in MT parameter estimates (P < .001) when unmodeled CEST data are included in the analysis., Conclusions: These results indicate that current practices of simultaneously fitting both CEST and MT effects in model-based analyses can lead to significant bias in all parameter estimates unless a sufficiently detailed model is utilized. Therefore, care must be taken when quantifying CEST and MT effects in vivo by properly modeling data to minimize these biases., (© 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Inorganic polyphosphate (polyP) is the polymer of phosphate. Water-soluble polyPs with average chain lengths of 2-40 P-subunits are widely used as food additives and are currently synthesized chemically. An environmentally friendly highly scalable process to biosynthesize water-soluble food-grade polyP in powder form (termed bio-polyP) is presented in this study. After incubation in a phosphate-free medium, generally regarded as safe wild-type baker's yeast (Saccharomyces cerevisiae) took up phosphate and intracellularly polymerized it into 26.5% polyP (as KPO 3 , in cell dry weight). The cells were lyzed by freeze-thawing and gentle heat treatment (10 min, 70°C). Protein and nucleic acid were removed from the soluble cell components by precipitation with 50 mM HCl. Two chain length fractions (42 and 11P-subunits average polyP chain length, purity on a par with chemically produced polyP) were obtained by fractional polyP precipitation (Fraction 1 was precipitated with 100 mM NaCl and 0.15 vol ethanol, and Fraction 2 with 1 final vol ethanol), drying, and milling. The physicochemical properties of bio-polyP were analyzed with an enzyme assay, 31 P nuclear magnetic resonance spectroscopy, and polyacrylamide gel electrophoresis, among others. An envisaged application of the process is phosphate recycling from waste streams into high-value bio-polyP., (© 2020 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals, Inc.)

Premise: Large genomic data sets offer the promise of resolving historically recalcitrant species relationships. However, different methodologies can yield conflicting results, especially when clades have experienced ancient, rapid diversification. Here, we analyzed the ancient radiation of Ericales and explored sources of uncertainty related to species tree inference, conflicting gene tree signal, and the inferred placement of gene and genome duplications., Methods: We used a hierarchical clustering approach, with tree-based homology and orthology detection, to generate six filtered phylogenomic matrices consisting of data from 97 transcriptomes and genomes. Support for species relationships was inferred from multiple lines of evidence including shared gene duplications, gene tree conflict, gene-wise edge-based analyses, concatenation, and coalescent-based methods, and is summarized in a consensus framework., Results: Our consensus approach supported a topology largely concordant with previous studies, but suggests that the data are not capable of resolving several ancient relationships because of lack of informative characters, sensitivity to methodology, and extensive gene tree conflict correlated with paleopolyploidy. We found evidence of a whole-genome duplication before the radiation of all or most ericalean families, and demonstrate that tree topology and heterogeneous evolutionary rates affect the inferred placement of genome duplications., Conclusions: We provide several hypotheses regarding the history of Ericales, and confidently resolve most nodes, but demonstrate that a series of ancient divergences are unresolvable with these data. Whether paleopolyploidy is a major source of the observed phylogenetic conflict warrants further investigation., (© 2020 Botanical Society of America.)

Clinicians involved with different aspects of the care of persons with multiple sclerosis (MS) and scientists with expertise on clinical and imaging techniques convened in Dallas, TX, USA on February 27, 2019 at a North American Imaging in Multiple Sclerosis Cooperative workshop meeting. The aim of the workshop was to discuss cardinal pathobiological mechanisms implicated in the progression of MS and novel imaging techniques, beyond brain atrophy, to unravel these pathologies. Indeed, although brain volume assessment demonstrates changes linked to disease progression, identifying the biological mechanisms leading up to that volume loss are key for understanding disease mechanisms. To this end, the workshop focused on the application of advanced magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging techniques to assess and measure disease progression in both the brain and the spinal cord. Clinical translation of quantitative MRI was recognized as of vital importance, although the need to maintain a relatively short acquisition time mandated by most radiology departments remains the major obstacle toward this effort. Regarding PET, the panel agreed upon its utility to identify ongoing pathological processes. However, due to costs, required expertise, and the use of ionizing radiation, PET was not considered to be a viable option for ongoing care of persons with MS. Collaborative efforts fostering robust study designs and imaging technique standardization across scanners and centers are needed to unravel disease mechanisms leading to progression and discovering medications halting neurodegeneration and/or promoting repair., (© 2020 by the American Society of Neuroimaging.)

Premise: Discordance between nuclear and organellar phylogenies (cytonuclear discordance) is a well-documented phenomenon at shallow evolutionary levels but has been poorly investigated at deep levels of plant phylogeny. Determining the extent of cytonuclear discordance across major plant lineages is essential not only for elucidating evolutionary processes, but also for evaluating the currently used framework of plant phylogeny, which is largely based on the plastid genome., Methods: We present a phylogenomic examination of a major angiosperm clade (Asteridae) based on sequence data from the nuclear, plastid, and mitochondrial genomes as a means of evaluating currently accepted relationships inferred from the plastome and exploring potential sources of genomic conflict in this group., Results: We recovered at least five instances of well-supported cytonuclear discordance concerning the placements of major asterid lineages (i.e., Ericales, Oncothecaceae, Aquifoliales, Cassinopsis, and Icacinaceae). We attribute this conflict to a combination of incomplete lineage sorting and hybridization, the latter supported in part by previously inferred whole-genome duplications., Conclusions: Our results challenge several long-standing hypotheses of asterid relationships and have implications for morphological character evolution and for the importance of ancient whole-genome duplications in early asterid evolution. These findings also highlight the value of reevaluating broad-scale angiosperm and green-plant phylogeny with nuclear genomic data., (© 2020 Botanical Society of America.)

Purpose: To measure the transverse relaxation time T 2 * in healthy human cervical spinal cord gray matter (GM) and white matter (WM) at 3T., Methods: Thirty healthy volunteers were recruited. Axial images were acquired using an averaged multi-echo gradient-echo (mFFE) T 2 *-weighted sequence with 5 echoes. We used the signal equation for an mFFE sequence with constant dephasing gradients after each echo to jointly estimate the spin density and T 2 * for each voxel., Results: No global difference in T 2 * was observed between all GM (41.3 ± 5.6 ms) and all WM (39.8 ± 5.4 ms). No significant differences were observed between left (43.2 ± 6.8 ms) and right (43.4 ± 5.5 ms) ventral GM, left (38.3 ± 6.1 ms) and right (38.6 ± 6.5 ms) dorsal GM, and left (39.4 ± 5.8 ms) and right (40.3 ± 5.8 ms) lateral WM. However, significant regional differences were observed between ventral (43.4 ± 5.7 ms) and dorsal (38.4 ± 6.0 ms) GM (p < 0.05), as well as between ventral (42.9 ± 6.5 ms) and dorsal (37.9 ± 6.2 ms) WM (p < 0.05). In analyses across slices, inferior T 2 * was longer than superior T 2 * in GM (44.7 ms vs. 40.1 ms; p < 0.01) and in WM (41.8 ms vs. 35.9 ms; p < 0.01)., Conclusions: Significant differences in T 2 * are observed between ventral and dorsal GM, ventral and dorsal WM, and superior and inferior GM and WM. There is no evidence for bilateral asymmetry in T 2 * in the healthy cord. These values of T 2 * in the spinal cord are notably lower than most reported values of T 2 * in the cortex., (© 2019 International Society for Magnetic Resonance in Medicine.)

Purpose: The non-uniform fast Fourier transform (NUFFT) involves interpolation of non-uniformly sampled Fourier data onto a Cartesian grid, an interpolation that is slowed by complex, non-local data access patterns. A faster NUFFT would increase the clinical relevance of the plethora of advanced non-Cartesian acquisition methods., Methods: Here we customize the NUFFT procedure for a radial trajectory and GPU architecture to eliminate the bottlenecks encountered when allowing for arbitrary trajectories and hardware. We call the result TRON, for TRajectory Optimized NUFFT. We benchmark the speed and accuracy TRON on a Shepp-Logan phantom and on whole-body continuous golden-angle radial MRI., Results: TRON was 6-30× faster than the closest competitor, depending on test data set, and was the most accurate code tested., Conclusions: Specialization of the NUFFT algorithm for a particular trajectory yielded significant speed gains. TRON can be easily extended to other trajectories, such as spiral and PROPELLER. TRON can be downloaded at http://github.com/davidssmith/TRON., (© 2018 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To optimize a selective inversion recovery (SIR) sequence for macromolecular content mapping in the human brain at 3.0T., Theory and Methods: SIR is a quantitative method for measuring magnetization transfer (qMT) that uses a low-power, on-resonance inversion pulse. This results in a biexponential recovery of free water signal that can be sampled at various inversion/predelay times (t I/ t D ) to estimate a subset of qMT parameters, including the macromolecular-to-free pool-size-ratio (PSR), the R 1 of free water (R 1f ), and the rate of MT exchange (k mf ). The adoption of SIR has been limited by long acquisition times (≈4 min/slice). Here, we use Cramér-Rao lower bound theory and data reduction strategies to select optimal t I /t D combinations to reduce imaging times. The schemes were experimentally validated in phantoms, and tested in healthy volunteers (N = 4) and a multiple sclerosis patient., Results: Two optimal sampling schemes were determined: (i) a 5-point scheme (k mf estimated) and (ii) a 4-point scheme (k mf assumed). In phantoms, the 5/4-point schemes yielded parameter estimates with similar SNRs as our previous 16-point scheme, but with 4.1/6.1-fold shorter scan times. Pair-wise comparisons between schemes did not detect significant differences for any scheme/parameter. In humans, parameter values were consistent with published values, and similar levels of precision were obtained from all schemes. Furthermore, fixing k mf reduced the sensitivity of PSR to partial-volume averaging, yielding more consistent estimates throughout the brain., Conclusions: qMT parameters can be robustly estimated in ≤1 min/slice (without independent measures of ΔB 0 , B1+, and T 1 ) when optimized t I -t D combinations are selected., (© 2018 International Society for Magnetic Resonance in Medicine.)

A tintinnid ciliate isolated from waters of the Thames River (Connecticut, USA) is described through combined in vivo observation, protargol impregnation, and phylogenetic analysis. The novel genus Dartintinnus and its type species, D. alderae are distinct from established tintinnid taxa by a lorica that collapses on both anterior and posterior ends. Dartintinnus is placed in the family Eutintinnidae based on a hyaline, elongated lorica opened at both ends, a ciliary pattern including a ventral kinety, at least one dorsal kinety, and right, left and lateral fields, and a sister relationship with Eutintinnus in gene trees. Main differences between D. alderae and Eutintinnus species include a 5.5-6.5% divergence in the small subunit rRNA gene, the geometry of the lorica (resembling an isosceles tetrahedron when collapsed vs. a cylinder, respectively), the number of macronuclear nodules (two vs. four), and the number of dorsal kineties (one vs. usually two). Considering the features of the new genus, we improve the diagnosis of the family Eutintinnidae, including the presence of a lateral ciliary field that had been overlooked in some Eutintinnus species. This work exemplifies the potential for novel diversity, even in these relatively well-studied protists, and the importance of an integrated approach for the description of tintinnid taxa., (© 2017 The Author(s) Journal of Eukaryotic Microbiology © 2017 International Society of Protistologists.)

The purpose of this work was to evaluate the feasibility and reproducibility of the spherical mean technique (SMT), a multi-compartmental diffusion model, in the spinal cord of healthy controls, and to assess its ability to improve spinal cord characterization in multiple sclerosis (MS) patients at 3 T. SMT was applied in the cervical spinal cord of eight controls and six relapsing-remitting MS patients. SMT provides an elegant framework to model the apparent axonal volume fraction v ax , intrinsic diffusivity D ax , and extra-axonal transverse diffusivity D ex&#95;perp (which is estimated as a function of v ax and D ax ) without confounds related to complex fiber orientation distribution that reside in diffusion MRI modeling. SMT's reproducibility was assessed with two different scans within a month, and SMT-derived indices in healthy and MS cohorts were compared. The influence of acquisition scheme on SMT was also evaluated. SMT's v ax , D ax , and D ex&#95;perp measurements all showed high reproducibility. A decrease in v ax was observed at the site of lesions and normal appearing white matter (p < 0.05), and trends towards a decreased D ax and increased D ex&#95;perp were seen. Importantly, a twofold reduction in acquisition yielded similarly high accuracy with SMT. SMT provides a fast, reproducible, and accurate method to improve characterization of the cervical spinal cord, and may have clinical potential for MS patients., (Copyright © 2018 John Wiley & Sons, Ltd.)

Premise of the Study: Large phylogenies can help shed light on macroevolutionary patterns that inform our understanding of fundamental processes that shape the tree of life. These phylogenies also serve as tools that facilitate other systematic, evolutionary, and ecological analyses. Here we combine genetic data from public repositories (GenBank) with phylogenetic data (Open Tree of Life project) to construct a dated phylogeny for seed plants., Methods: We conducted a hierarchical clustering analysis of publicly available molecular data for major clades within the Spermatophyta. We constructed phylogenies of major clades, estimated divergence times, and incorporated data from the Open Tree of Life project, resulting in a seed plant phylogeny. We estimated diversification rates, excluding those taxa without molecular data. We also summarized topological uncertainty and data overlap for each major clade., Key Results: The trees constructed for Spermatophyta consisted of 79,881 and 353,185 terminal taxa; the latter included the Open Tree of Life taxa for which we could not include molecular data from GenBank. The diversification analyses demonstrated nested patterns of rate shifts throughout the phylogeny. Data overlap and inference uncertainty show significant variation throughout and demonstrate the continued need for data collection across seed plants., Conclusions: This study demonstrates a means for combining available resources to construct a dated phylogeny for plants. However, this approach is an early step and more developments are needed to add data, better incorporating underlying uncertainty, and improve resolution. The methods discussed here can also be applied to other major clades in the tree of life., (© 2018 Smith and Brown American Journal of Botany is published by Wiley Periodicals, Inc. on behalf of the Botanical Society of America.)

Premise of the Study: Phylogenetic support has been difficult to evaluate within the green plant tree of life partly due to a lack of specificity between conflicted versus poorly informed branches. As data sets continue to expand in both breadth and depth, new support measures are needed that are more efficient and informative., Methods: We describe the Quartet Sampling (QS) method, a quartet-based evaluation system that synthesizes several phylogenetic and genomic analytical approaches. QS characterizes discordance in large-sparse and genome-wide data sets, overcoming issues of alignment sparsity and distinguishing strong conflict from weak support. We tested QS with simulations and recent plant phylogenies inferred from variously sized data sets., Key Results: QS scores demonstrated convergence with increasing replicates and were not strongly affected by branch depth. Patterns of QS support from different phylogenies led to a coherent understanding of ancestral branches defining key disagreements, including the relationships of Ginkgo to cycads, magnoliids to monocots and eudicots, and mosses to liverworts. The relationships of ANA-grade angiosperms (Amborella, Nymphaeales, Austrobaileyales), major monocot groups, bryophytes, and fern families are likely highly discordant in their evolutionary histories, rather than poorly informed. QS can also detect discordance due to introgression in phylogenomic data., Conclusions: Quartet Sampling is an efficient synthesis of phylogenetic tests that offers more comprehensive and specific information on branch support than conventional measures. The QS method corroborates growing evidence that phylogenomic investigations that incorporate discordance testing are warranted when reconstructing complex evolutionary histories, in particular those surrounding ANA-grade, monocots, and nonvascular plants., (© 2018 The Authors. American Journal of Botany is published by Wiley Periodicals, Inc. on behalf of the Botanical Society of America.)

Premise of the Study: Discordant gene trees are commonly encountered when sequences from thousands of loci are applied to estimate phylogenetic relationships. Several processes contribute to this discord. Yet, we have no methods that jointly model different sources of conflict when estimating phylogenies. An alternative to analyzing entire genomes or all the sequenced loci is to identify a subset of loci for phylogenetic analysis. If we can identify data partitions that are most likely to reflect descent from a common ancestor (i.e., discordant loci that indeed reflect incomplete lineage sorting [ILS], as opposed to some other process, such as lateral gene transfer [LGT]), we can analyze this subset using powerful coalescent-based species-tree approaches., Methods: Test data sets were simulated where discord among loci could arise from ILS and LGT. Data sets where analyzed using the newly developed program CLASSIPHY (Huang et al., ) to assess whether our ability to distinguish the cause of discord among loci varied when ILS and LGT occurred in the recent versus deep past and whether the accuracy of these inferences were affected by the mutational process., Key Results: We show that accuracy of probabilistic classification of individual loci by the cause of discord differed when ILS and LGT events occurred more recently compared with the distant past and that the signal-to-noise ratio arising from the mutational process contributes to difficulties in inferring LGT data partitions., Conclusions: We discuss our findings in terms of the promise and limitations of identifying subsets of loci for species-tree inference that will not violate the underlying coalescent model (i.e., data partitions in which ILS, and not LGT, contributes to discord). We also discuss the empirical implications of our work given the many recalcitrant nodes in the tree of life (e.g., origins of angiosperms, amniotes, or Neoaves), and recent arguments for concatenating loci., (© 2018 Botanical Society of America.)

Providing science and society with an integrated, up-to-date, high quality, open, reproducible and sustainable plant tree of life would be a huge service that is now coming within reach. However, synthesizing the growing body of DNA sequence data in the public domain and disseminating the trees to a diverse audience are often not straightforward due to numerous informatics barriers. While big synthetic plant phylogenies are being built, they remain static and become quickly outdated as new data are published and tree-building methods improve. Moreover, the body of existing phylogenetic evidence is hard to navigate and access for non-experts. We propose that our community of botanists, tree builders, and informaticians should converge on a modular framework for data integration and phylogenetic analysis, allowing easy collaboration, updating, data sourcing and flexible analyses. With support from major institutions, this pipeline should be re-run at regular intervals, storing trees and their metadata long-term. Providing the trees to a diverse global audience through user-friendly front ends and application development interfaces should also be a priority. Interactive interfaces could be used to solicit user feedback and thus improve data quality and to coordinate the generation of new data. We conclude by outlining a number of steps that we suggest the scientific community should take to achieve global phylogenetic synthesis., (© 2018 Botanical Society of America.)

Using phylogenetic approaches to test hypotheses on a large scale, in terms of both species sampling and associated species traits and occurrence data-and doing this with rigor despite all the attendant challenges-is critical for addressing many broad questions in evolution and ecology. However, application of such approaches to empirical systems is hampered by a lingering series of theoretical and practical bottlenecks. The community is still wrestling with the challenges of how to develop species-level, comprehensively sampled phylogenies and associated geographic and phenotypic resources that enable global-scale analyses. We illustrate difficulties and opportunities using the rosids as a case study, arguing that assembly of biodiversity data that is scale-appropriate-and therefore comprehensive and global in scope-is required to test global-scale hypotheses. Synthesizing comprehensive biodiversity data sets in clades such as the rosids will be key to understanding the origin and present-day evolutionary and ecological dynamics of the angiosperms., (© 2018 The Authors. American Journal of Botany is published by Wiley Periodicals, Inc. on behalf of the Botanical Society of America.)

Premise of the Study: The Caryophyllales contain ~12,500 species and are known for their cosmopolitan distribution, convergence of trait evolution, and extreme adaptations. Some relationships within the Caryophyllales, like those of many large plant clades, remain unclear, and phylogenetic studies often recover alternative hypotheses. We explore the utility of broad and dense transcriptome sampling across the order for resolving evolutionary relationships in Caryophyllales., Methods: We generated 84 transcriptomes and combined these with 224 publicly available transcriptomes to perform a phylogenomic analysis of Caryophyllales. To overcome the computational challenge of ortholog detection in such a large data set, we developed an approach for clustering gene families that allowed us to analyze >300 transcriptomes and genomes. We then inferred the species relationships using multiple methods and performed gene-tree conflict analyses., Key Results: Our phylogenetic analyses resolved many clades with strong support, but also showed significant gene-tree discordance. This discordance is not only a common feature of phylogenomic studies, but also represents an opportunity to understand processes that have structured phylogenies. We also found taxon sampling influences species-tree inference, highlighting the importance of more focused studies with additional taxon sampling., Conclusions: Transcriptomes are useful both for species-tree inference and for uncovering evolutionary complexity within lineages. Through analyses of gene-tree conflict and multiple methods of species-tree inference, we demonstrate that phylogenomic data can provide unparalleled insight into the evolutionary history of Caryophyllales. We also discuss a method for overcoming computational challenges associated with homolog clustering in large data sets., (© 2018 The Authors. American Journal of Botany is published by Wiley Periodicals, Inc. on behalf of the Botanical Society of America.)

Purpose: The ability to evaluate pathological changes in the spinal cord in multiple sclerosis (MS) is limited because T 1 - and T 2 -w MRI imaging are not sensitive to biochemical changes in vivo. Amide proton transfer (APT) chemical exchange saturation transfer (CEST) can indirectly detect amide protons associated with proteins and peptides, potentially providing more pathological specificity. Here, we implement APT CEST in the cervical spinal cord of healthy and MS cohorts at 3T., Methods: APT CEST of the cervical spinal cord was obtained in a cohort of 10 controls and 10 MS patients using a novel respiratory correction methodology. APT was quantified using two methods: 1) APT w , based off the conventional magnetization transfer ratio asymmetry, and 2) ΔAPT, a spatial characterization of APT changes in MS patients relative to the controls., Results: Respiratory correction yielded highly reproducible z-spectra in white matter (intraclass correlation coefficient = 0.82). APT w signals in normal-appearing white matter (NAWM) of MS patients were significantly different from healthy controls (P = 0.04), whereas ΔAPT of MS patients highlighted large APT differences in NAWM., Conclusion: Respiration correction in the spinal cord is necessary to accurately quantify APT CEST, which can provide unique biochemical information regarding disease processes within the spinal cord. Magn Reson Med 79:806-814, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: To investigate the physical mechanisms associated with the contrast observed in neuromelanin MRI., Methods: Phantoms having different concentrations of synthetic melanins with different degrees of iron loading were examined on a 3 Tesla scanner using relaxometry and quantitative magnetization transfer (MT)., Results: Concentration-dependent T 1 and T 2 shortening was most pronounced for the melanin pigment when combined with iron. Metal-free melanin had a negligible effect on the magnetization transfer spectra. On the contrary, the presence of iron-laden melanins resulted in a decreased magnetization transfer ratio. The presence of melanin or iron (or both) did not have a significant effect on the macromolecular content, represented by the pool size ratio., Conclusion: The primary mechanism underlying contrast in neuromelanin-MRI appears to be the T 1 reduction associated with melanin-iron complexes. The macromolecular content is not significantly influenced by the presence of melanin with or without iron, and thus the MT is not directly affected. However, as T 1 plays a role in determining the MT-weighted signal, the magnetization transfer ratio is reduced in the presence of melanin-iron complexes. Magn Reson Med 78:1790-1800, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Premise of Study: The carnivorous members of the large, hyperdiverse Caryophyllales (e.g., Venus flytrap, sundews, and Nepenthes pitcher plants) represent perhaps the oldest and most diverse lineage of carnivorous plants. However, despite numerous studies seeking to elucidate their evolutionary relationships, the early-diverging relationships remain unresolved., Methods: To explore the utility of phylogenomic data sets for resolving relationships among the carnivorous Caryophyllales, we sequenced 10 transcriptomes, including all the carnivorous genera except those in the rare West African liana family Dioncophyllaceae. We used a variety of methods to infer the species tree, examine gene tree conflict, and infer paleopolyploidy events., Key Results: Phylogenomic analyses supported the monophyly of the carnivorous Caryophyllales, with a crown age of 68-83 million years. In contrast to previous analyses, we recovered the remaining noncore Caryophyllales as nonmonophyletic, although the node supporting this relationship contained a significant amount of gene tree discordance. We present evidence that the clade contains at least seven independent paleopolyploidy events, previously unresolved nodes from the literature have high levels of gene tree conflict, and taxon sampling influences topology even in a phylogenomic data set, regardless of the use of coalescent or supermatrix methods., Conclusions: Our data demonstrate the importance of carefully considering gene tree conflict and taxon sampling in phylogenomic analyses. Moreover, they provide a remarkable example of the propensity for paleopolyploidy in angiosperms, with at least seven such events in a clade of less than 2500 species., (© 2017 Walker et al. Published by the Botanical Society of America. This work is licensed under a Creative Commons Attribution License (CC-BY).)

Purpose: The optic nerve (ON) represents the sole pathway between the eyes and brain; consequently, diseases of the ON can have dramatic effects on vision. However, quantitative magnetization transfer (qMT) applications in the ON have been limited to ex vivo studies, in part because of the fatty connective tissue that surrounds the ON, confounding the magnetization transfer (MT) experiment. Therefore, the aim of this study was to implement a multi-echo Dixon fat-water separation approach to remove the fat component from MT images., Methods: MT measurements were taken in a single slice of the ON and frontal lobe using a three-echo Dixon readout, and the water and out-of-phase images were applied to a two-pool model in ON tissue and brain white matter to evaluate the effectiveness of using Dixon fat-water separation to remove fatty tissue from MT images., Results: White matter data showed no significant differences between image types; however, there was a significant increase (p < 0.05) in variation in the out-of-phase images in the ON relative to the water images., Conclusions: The results of this study demonstrate that Dixon fat-water separation can be robustly used for accurate MT quantification of anatomies susceptible to partial volume effects resulting from fat. Magn Reson Med 77:707-716, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

High-magnetic-field (7 T) chemical exchange saturation transfer (CEST) MRI provides information on the tissue biochemical environment. Multiple sclerosis (MS) affects the entire central nervous system, including the spinal cord. Optimal CEST saturation parameters found via simulation were implemented for CEST MRI in 10 healthy controls and 10 patients with MS, and the results were examined using traditional asymmetry analysis and a Lorentzian fitting method. In addition, T1 - and T2 *-weighted images were acquired for lesion localization and the transmitted B1 (+) field was evaluated to guide imaging parameters. Distinct spectral features for all tissue types studied were found both up- and downfield from the water resonance. The z spectra in healthy subjects had the expected z spectral shape with CEST effects apparent from 2.0 to 4.5 ppm. The z spectra from patients with MS demonstrated deviations from this expected normal shape, indicating this method's sensitivity to known pathology as well as to tissues appearing normal on conventional MRI. Examination of the calculated CESTasym revealed increased asymmetry around the amide proton resonance (Δω = 3.5 ppm), but it was apparent that this measure is complicated by detail in the CEST spectrum upfield from water, which is expected to result from the nuclear Overhauser effect. The z spectra upfield (negative ppm range) were also distinct between healthy and diseased tissue, and could not be ignored, particularly when considering the conventional asymmetry analysis used to quantify the CEST effect. For all frequencies greater than +1 ppm, the Lorentzian differences (and z spectra) for lesions and normal-appearing white matter were distinct from those for healthy white matter. The increased frequency separation and signal-to-noise ratio, in concert with prolonged T1 at 7 T, resulted in signal enhancements necessary to detect subtle tissue changes not possible at lower field strengths. This study presents CEST imaging metrics that may be sensitive to the extensive and temporally varying biochemical neuropathology of MS in the spinal cord. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Purpose: To develop a chemical exchange saturation transfer (CEST) scheme sensitive to hydroxyl protons at 3 T. Clinical imaging of hydroxyl moieties can have an impact on osteoarthritis, neuropsychiatric disorders, and cancer., Theory: By varying saturation amplitude linearly with frequency offset, the direct water saturation component of the Z-spectrum is flattened and can be subtracted to produce a magnetization transfer ratio difference spectrum (MTRdiff ) that isolates solute resonances. Variable saturation power allows for near optimization of hydroxyl and amine/amide moieties in one Z-spectrum., Methods: Phantom studies were used to test vCEST performance in two environments: (1) aqueous single-solute (glycogen, glucose); (2) aqueous multiple solute (glycogen with bovine serum albumin). In vivo vCEST imaging of glycosaminoglycan content in patellar-femoral cartilage was performed in a subject with history of cartilage transplant., Results: In solutions with overlapping resonances, vCEST resolves separate hydroxyl and amine/amide peaks. CEST hydroxyl signal in cartilage is negligible, but with vCEST, hydroxyl signal ranged from 2 to 5% ppm and showed distinct contrast between lesions and normal appearing cartilage., Conclusion: Introduced a variable saturation amplitude CEST (vCEST) scheme to improve sensitivity to exchangeable hydroxyl moieties at 3 T resulting in detection of hydroxyl in the presence of multiple solutes with overlapping resonances. Magn Reson Med 76:826-837, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Purpose: Our goal is to develop an accurate, automated tool to characterize the optic nerve (ON) and cerebrospinal fluid (CSF) to better understand ON changes in disease., Methods: Multi-atlas segmentation is used to localize the ON and sheath on T2-weighted MRI (0.6 mm(3) resolution). A sum of Gaussian distributions is fit to coronal slice-wise intensities to extract six descriptive parameters, and a regression forest is used to map the model space to radii. The model is validated for consistency using tenfold cross-validation and for accuracy using a high resolution (0.4 mm(2) reconstructed to 0.15 mm(2)) in vivo sequence. We evaluated this model on 6 controls and 6 patients with multiple sclerosis (MS) and a history of optic neuritis., Results: In simulation, the model was found to have an explanatory R-squared for both ON and sheath radii greater than 0.95. The accuracy of the method was within the measurement error on the highest possible in vivo resolution. Comparing healthy controls and patients with MS, significant structural differences were found near the ON head and the chiasm, and structural trends agreed with the literature., Conclusion: This is a first demonstration that the ON can be exclusively, quantitatively measured and separated from the surrounding CSF using MRI., (© 2015 Wiley Periodicals, Inc.)

Purpose: Lymphatic impairment is known to reduce quality of life in some of the most crippling diseases of the 21st century, including obesity, lymphedema, and cancer. However, the lymphatics are not nearly as well-understood as other bodily systems, largely owing to a lack of sensitive imaging technologies that can be applied using standard clinical equipment. Here, proton exchange-weighted MRI is translated to the lymphatics in patients with breast cancer treatment-related lymphedema (BCRL)., Methods: Healthy volunteers (N = 8) and BCRL patients (N = 7) were scanned at 3 Tesla using customized structural MRI and amide proton transfer (APT) chemical exchange saturation transfer (CEST) MRI in sequence with the hypothesis that APT effects would be elevated in lymphedematous tissue. APT contrast, lymphedema stage, symptomatology, and histology information were evaluated., Results: No significant difference between proton-weighted APT contrast in the right and left arms of healthy controls was observed. An increase in APT contrast in the affected arms of patients was found (P = 0.025; Cohen's d = 2.4), and variability among patients was consistent with documented damage to lymphatics as quantified by lymphedema stage., Conclusion: APT CEST MRI may have relevance for evaluating lymphatic impairment in patients with BCRL, and may extend to other pathologies where lymphatic compromise is evident., (© 2015 Wiley Periodicals, Inc.)

Purpose: A diffusion-weighted multishot echo-planar imaging approach combined with SENSE and a two-dimensional (2D) navigated motion correction was investigated as an alternative to conventional single-shot counterpart to obtain optic nerve images at higher spatial resolution with reduced artifacts., Methods: Fifteen healthy subjects were enrolled in the study. Six of these subjects underwent a repeated acquisition at least 2 weeks after the initial scan session to address reproducibility. Both single-shot and multishot diffusion tensor imaging studies of the human optic nerve were performed with matched scan time. Effect of subject motions were corrected using 2D phase navigator during multishot image reconstruction. Tensor-derived indices from proposed multishot were compared against conventional single-shot approach. Image resolution difference, right-left optic nerve asymmetry, and test-retest reproducibility were also assessed., Results: In vivo results of acquired multishot images and quantitative maps of diffusion properties of the optic nerve showed significantly reduced image artifacts (e.g., distortions and blurring), and the derived diffusion indices were comparable to those from other studies. Single-shot scans presented larger variability between right and left optic nerves than multishot scans. Multishot scans also presented smaller variations across scans at different time points when compared with single-shot counterparts., Conclusion: The multishot technique has considerable potential for providing improved information on optic nerve pathology and may also be translated to higher fields., (© 2014 Wiley Periodicals, Inc.)

Objectives: Constipation is a common and potentially serious side effect of oral opioids. Accordingly, most clinical guidelines suggest routine use of laxatives to prevent opioid-induced constipation. The objective was to characterize emergency provider prescribing of laxatives to prevent constipation among adults initiating outpatient opioid treatment., Methods: National Hospital Ambulatory Medical Care Survey (NHAMCS) data from 2010 were analyzed. Among visits by individuals aged 18 years and older discharged from the emergency department (ED) with opioid prescriptions, the authors estimated the survey-weighted proportion of visits in which laxatives were also prescribed. A subgroup analysis was conducted for individuals aged 65 years and older, as the potential risks associated with opioid-induced constipation are greater among older individuals. To examine a group expected to be prescribed laxative medication and confirm that NHAMCS captures prescriptions for these medications, the authors estimated the proportion of visits by individuals discharged with prescriptions for laxatives among those who presented with constipation., Results: Among visits in 2010 by adults aged 18 years and older discharged from the ED with opioid prescriptions, 0.9% (95% confidence interval [CI] = 0.7% to 1.3%, estimated total n = 191,203 out of 21,075,050) received prescriptions for laxatives. Among the subset of visits by adults aged 65 years and older, 1.0% (95% CI = 0.5% to 2.0%, estimated total n = 18,681 out of 1,904,411) received prescriptions for laxatives. In comparison, among visits by individuals aged 18 years and older with constipation as a reason for visit, 42% received prescriptions for laxatives., Conclusions: In this nationally representative sample, laxatives were not routinely prescribed to adults discharged from the ED with prescriptions for opioid pain medications. Routine prescribing of laxatives for ED visits may improve the safety and effectiveness of outpatient opioid pain management., (© 2015 by the Society for Academic Emergency Medicine.)

Background: The high value of the specific absorption rate (SAR) of radio-frequency (RF) energy arising from the series of RF refocusing pulses in T2-weighted (T2-w) turbo spin echo (TSE) MRI hampers its clinical application at 7.0 Tesla (7T). T2-w gradient and spin echo (GRASE) uses the speed from gradient refocusing in combination with the chemical-shift/static magnetic field (B0) inhomogeneity insensitivity from spin-echo refocusing to acquire T2-w images with a limited number of refocusing RF pulses, thus reducing SAR., Objectives: To investigate whether low SAR T2-w GRASE could replace T2-w TSE in detecting white matter (WM) disease in MS patients imaged at 7T., Methods: The .7 mm3 isotropic T2-w TSE and T2-w GRASE images with variable echo times (TEs) and echo planar imaging (EPI) factors were obtained on a 7T scanner from postmortem samples of MS brains. These samples were derived from brains of 3 female MS patients. WM lesions (WM-Ls) and normal-appearing WM (NAWM) signal intensity, WM-Ls/NAWM contrast-to-noise ratio (CNR) and MRI/myelin staining sections comparisons were obtained., Results: GRASE sequences with EPI factor/TE = 3/50 and 3/75 ms were comparable to the SE technique for measures of CNR in WM-Ls and NAWM and for detection of WM-Ls. In all sequences, however, identification of areas with remyelination, Wallerian degeneration, and gray matter demyelination, as depicted by myelin staining, was not possible., Conclusions: T2-w GRASE images may replace T2-w TSE for clinical use. However, even at 7T, both sequences fail in detecting and characterizing MS disease beyond visible WM-Ls., (Copyright © 2015 by the American Society of Neuroimaging.)

Purpose: This critical literature review explored the current state of the science regarding mindfulness-based stress reduction (MBSR) as a potential intervention to improve the ability of nurses to effectively cope with stress., Methods: Literature sources include searches from EBSCOhost, Gale PowerSearch, ProQuest, PubMed Medline, Google Scholar, Online Journal of Issues in Nursing, and reference lists from relevant articles., Findings: Empirical evidence regarding utilizing MBSR with nurses and other healthcare professionals suggests several positive benefits including decreased stress, burnout, and anxiety; and increased empathy, focus, and mood., Conclusions: Nurse use of MBSR may be a key intervention to help improve nurses' ability to cope with stress and ultimately improve the quality of patient care provided., (© 2014 NANDA International, Inc.)

Chemical exchange saturation transfer (CEST)-derived, pH-weighted, amide proton transfer (APT) MRI has shown promise in animal studies for the prediction of infarction risk in ischemic tissue. Here, APT MRI was translated to patients with acute stroke (1-24 h post-symptom onset), and assessments of APT contrast, perfusion, diffusion, disability and final infarct volume (23-92 days post-stroke) are reported. Healthy volunteers (n = 5) and patients (n = 10) with acute onset of symptoms (0-4 h, n = 7; uncertain onset <24 h, n = 3) were scanned with diffusion- and perfusion-weighted MRI, fluid-attenuated inversion recovery (FLAIR) and CEST. Traditional asymmetry and a Lorentzian-based APT index were calculated in the infarct core, at-risk tissue (time-to-peak, TTP; lengthening) and final infarct volume. On average (mean ± standard deviation), control white matter APT values (asymmetry, 0.019 ± 0.005; Lorentzian, 0.045 ± 0.006) were not significantly different (p > 0.05) from APT values in normal-appearing white matter (NAWM) of patients (asymmetry, 0.022 ± 0.003; Lorentzian, 0.048 ± 0.003); however, ischemic regions in patients showed reduced (p = 0.03) APT effects compared with NAWM. Representative cases are presented, whereby the APT contrast is compared quantitatively with contrast from other imaging modalities. The findings vary between patients; in some patients, a trend for a reduction in the APT signal in the final infarct region compared with at-risk tissue was observed, consistent with tissue acidosis. However, in other patients, no relationship was observed in the infarct core and final infarct volume. Larger clinical studies, in combination with focused efforts on sequence development at clinically available field strengths (e.g. 3.0 T), are necessary to fully understand the potential of APT imaging for guiding the hyperacute management of patients., (Copyright © 2013 John Wiley & Sons, Ltd.)

Chemical exchange saturation transfer (CEST) can offer information about protons associated with mobile proteins through the amide proton transfer (APT) effect, which has been shown to discriminate tumor from healthy tissue and, more recently, has been suggested as a prognosticator of response to therapy. Despite this promise, APT effects are small (only a few percent of the total signal), and APT imaging is often prone to artifacts resulting from system instability. Here we present a procedure that enables the detection of APT effects in the human breast at 7T while mitigating these issues. Adequate signal-to-noise ratio (SNR) was achieved via an optimized quadrature RF breast coil and 3D acquisitions. To reduce the influence of fat, effective fat suppression schemes were developed that did not degrade SNR. To reduce the levels of ghosting artifacts, dummy scans have been integrated into the scanning protocol. Compared with results obtained at 3T, the standard deviation of the measured APT effect was reduced by a factor of four at 7T, allowing for the detection of APT effects with a standard deviation of 1% in the human breast at 7T. Together, these results demonstrate that the APT effect can be reliably detected in the healthy human breast with a high level of precision at 7T., (Copyright © 2013 John Wiley & Sons, Ltd.)