PURPOSE:This study sought to determine the variable effect of three cueing strategies (i.e., loud, clear, or slow speech) on speech intelligibility and perceived speech severity in talkers with dysarthria due to Parkinson's disease (PD). The study also aimed to identify perceptual speech features associated with responses to these speech cues. METHOD:Eighty-four naive listeners rated speech samples of 52 talkers with PD. Each talker's samples consisted of two sentences produced in habitual, loud, clear, and slow speech. Listeners rated intelligibility and speech severity as perceptual outcome measures using separate visual analog scales. The relative change in intelligibility and speech severity ratings from habitual speech to each speech cue was calculated. Based on the threshold of a meaningful change, talkers were grouped into "positive responders" and "nonpositive responders" for each outcome measure and each speech cue. Finally, a profile of perceptual speech features and severity ratings of the articulatory and phonatory subsystem impairment was established for each talker based on their habitual speech to identify potential predictors of the cueing response patterns. RESULTS:For both outcome measures, intelligibility and speech severity, loud speech elicited the most positive responses followed by clear speech and slow speech. Subsystem impairment severity differed between positive responders and non-positive responders. For each cueing strategy, the presence of specific perceptual speech features indicated a likelihood of a positive response. CONCLUSION:Findings provide an important stepping stone for future research that seeks to advance personalized treatment of dysarthria in talkers with PD.

INTRODUCTION:Glioblastoma is an aggressive brain tumor with poor survival rates and nearly universal recurrence. Magnetic resonance (MR) imaging obtained after radiation and chemotherapy treatment often shows "pseudoprogression" (PsP), or contrast enhancement that mimics tumor growth. However, this does not indicate actual disease progression. This study compared the efficacy of a previously developed radio-pathomic mapping model for discriminating between true progression (TP) and PsP relative to advanced diffusion and perfusion metrics. MATERIALS AND METHODS:This retrospective study utilized the UCSD-PTGBM single-site public dataset comprised of 171 MR imaging sessions (139 TP and 32 PsP) from 130 adult patients following initial biopsy or resection. Radio-pathomic maps of cell density (RPM Cell) and extracellular fluid density (RPM ECF) from a previously-established methodology were created using conventional imaging data (e.g., T1, T1C, FLAIR, ADC) from the public UCSD dataset. These maps were then compared to perfusion (rCBV, CBF, MTT) and restricted spectrum imaging (RSI) diffusion (Free, Hindered, Cell) features to assess differences between TP and PsP within regions of contrast enhancement. Statistical analyses involved Pearson correlation coefficients, mixed effect models, and receiver operator characteristic (ROC) analysis with area under the curve (AUC) used to evaluate performance at the first and all timepoints, using DeLong's tests to confirm significance. RESULTS:RPM Cell significantly (p=0.006) outperformed other imaging features in discriminating TP from PsP (AUC=0.827 vs. <0.687 for alternatives, across all timepoints). Features that differed between patients with TP and PsP included RPM Cell (B=5.71, p<0.001) and RSI Cell (B=2.54, p=0.01). CONCLUSION:RPM Cell shows promise as a novel, accessible marker for detecting tumor recurrence. These cell density maps outperform current advanced imaging techniques in distinguishing true tumor progression from PsP in a retrospective single-site dataset of glioblastoma patients, potentially offering clinicians valuable insights into the tumor microenvironment through a non-invasive modality without requiring additional contrast agents or scan time.

To examine the effect of deutetrabenazine on functional speech production and gait dynamics in individuals with Huntington's Disease (HD).

Although researchers have recognized the need to better account for the heterogeneous perceptual speech characteristics among talkers with the same disease, guidance on how to best establish such dysarthria subgroups is currently lacking. Therefore, we compared subgroup decisions of two data-driven approaches based on a cohort of talkers with Huntington’s disease (HD): (1) a statistical clustering approach (STATCLUSTER) based on perceptual speech characteristic profiles and (2) an auditory free classification approach (FREECLASS) based on listeners’ similarity judgments. We determined the amount of overlap across the two subgrouping decisions and the perceptual speech characteristics driving the subgrouping decisions of each approach. The same speech samples produced by 48 talkers with HD were used for both grouping approaches. The STATCLUSTER approach had been conducted previously. The FREECLASS approach was conducted in the present study. Both approaches yielded four dysarthria subgroups, which overlapped between 50% to 78%. In both grouping approaches, overall bizarreness and speech rate characteristics accounted for the grouping decisions. In addition, voice abnormalities contributed to the grouping decisions in the FREECLASS approach. These findings suggest that apart from overall bizarreness ratings, indexing dysarthria severity, speech rate and voice characteristics may be important features to establish dysarthria subgroups in HD.

OBJECTIVE:Despite the progressive advancement of devices for endovascular aortic repair (EVAR), endografts continue to fail, requiring explant. We present a single-institutional experience of EVAR explants, characterizing modern failure modes, presentation, and outcomes for partial and complete EVAR explantation. METHODS:A retrospective analysis was performed of all EVARs explanted at an urban quaternary center from 2001 to 2020, with one infected endograft excluded. Patient and graft characteristics, indications, and perioperative and long-term outcomes were analyzed. Partial versus complete explants were performed per surgeon discretion without a predefined protocol. This process was informed by patient risk factors; asymptomatic, symptomatic, or ruptured aneurysm presentation; and anatomical or intraoperative factors, including endoleak type. RESULTS:From 2001 to 2020, 52 explants met the inclusion and exclusion criteria. More than one-half (57.7%) were explants of EVAR devices placed at outside institutions, designated nonindex explants. Most patients were male (86.5%), the median age was 74 years (interquartile range, 70-78 years). More than one-half (61.5%) were performed in the second decade of the study period. The most commonly explanted grafts were Gore Excluder (n = 9 grafts), Cook Zenith (n = 8), Endologix AFX (n = 7), Medtronic Endurant (n = 5), and Medtronic Talent (n = 5). Most grafts (78.8%) were explanted for neck degeneration or sac expansion. Five were explanted for initial seal failure, five for symptomatic expansion, and seven for rupture. The median implant duration was 4.2 years, although ranging widely (interquartile range, 2.6-5.1 years), but similar between index and nonindex explants (4.2 years vs 4.1 years). Partial explantation was performed in 61.5%, with implant duration slightly lower, 3.2 years versus 4.4 years for complete explants. Partial explantation was more frequent in index explants (68.2% vs 56.7%). The median length of stay was 8 days. The median intensive care unit length of stay was 3 days, without significant differences in nonindex explants (4 days vs 3 days) and partial explants (4 days vs 3 days). Thirty-day mortality occurred in two nonindex explants (one partial and one complete explant). Thirty-day readmission was similar between partial and complete explants (9.7% vs 5.0%), without accounting for nonindex readmissions. Long-term survival was comparable between partial and complete explants in Cox regression (hazard ratio, 2.45; 95% confidence interval, 0.79-7.56; P = .12). CONCLUSIONS:Explants of EVAR devices have increased over time at our institution. Partial explant was performed in more than one-half of cases, per operating surgeon discretion, demonstrating higher blood loss, more frequent acute kidney injury, and longer intensive care unit stays, however with comparable short-term mortality and long-term survival.

Abstract BACKGROUND Recurrent glioblastoma (rGBM) patients are often treated with anti-angiogenic agents such as bevacizumab (BEV). Despite therapeutic promise, conventional MR methods fail to determine which patients may not benefit. PURPOSE: The purpose of this study was to utilize magnetic resonance spectroscopic imaging (MRSI) with intermediate and short echo time to generate corrected Myo-inositol normalized by contralateral creatine (mI/c-Cr) in patients with rGBM treated with BEV and investigate whether it can predict survivorship prior to BEV initiation (baseline) and at 1-day, 4-weeks, and 8-weeks thereafter. METHODS We conducted a prospective, longitudinal study and evaluated spectroscopic data of myo-inositol (mI), a glial marker and osmoregulator within the brain, normalized to contralateral-creatine (mI/c-Cr) in the intratumoral, contralateral normal appearing white matter, and peritumoral volumes of rGBM patients. Area under the ROC curve (AUC) was calculated for all volumes at baseline, 1-day, 4-weeks, and 8-weeks after treatment to determine mI/c-Cr’s ability to predict survivorship. RESULTS 21 participants (62 ± 12 years, 15 men) were evaluated. Lower mI/c-Cr in the tumor prior to and during BEV treatment predicted poor survivorship, with ROC analyses illustrating an AUC of 0.75 at baseline, 0.87 at 1-day, and 1 at 8 weeks. Lower levels of mI/c-Cr were also observed in the contralateral and the peritumoral volumes for shorter-term survivors. In the contralateral volume, lower mI/Cr was predictive of shorter-term survival at baseline and all other timepoints. Within the peritumoral volume, lower mI/c-Cr was predictive of shorter-term survival at baseline (AUC=0.80), 1-day (AUC=0.93), and 4-weeks (AUC=0.68). CONCLUSIONS Lower levels of mI/c-Cr within intratumoral, contralateral, and peritumoral volumes were predictive of poor survivorship and anti-angiogenic treatment failure as early as one month before BEV treatment. Acquiring MRSI alongside conventional MR imaging modalities can convey critical information regarding tumor microenvironment that informs management of patients with rGBM.

BACKGROUND:Determining failure to anti-angiogenic therapy in recurrent glioblastoma (GBM) (rGBM) remains a challenge. The purpose of the study was to assess treatment response to bevacizumab-based therapy in patients with rGBM using MR spectroscopy (MRS). METHODS:We performed longitudinal MRI/MRS in 33 patients with rGBM to investigate whether changes in N-acetylaspartate (NAA)/Choline (Cho) and Lactate (Lac)/NAA from baseline to subsequent time points after treatment can predict early failures to bevacizumab-based therapies. RESULTS:After stratifying based on 9-month survival, longer-term survivors had increased NAA/Cho and decreased Lac/NAA levels compared to shorter-term survivors. ROC analyses for intratumoral NAA/Cho correlated with survival at 1 day, 2 weeks, 8 weeks, and 16 weeks. Intratumoral Lac/NAA ROC analyses were predictive of survival at all time points tested. At the 8-week time point, 88% of patients with decreased NAA/Cho did not survive 9 months; furthermore, 90% of individuals with an increased Lac/NAA from baseline did not survive at 9 months. No other metabolic ratios tested significantly predicted survival. CONCLUSIONS:Changes in metabolic levels of tumoral NAA/Cho and Lac/NAA can serve as early biomarkers for predicting treatment failure to anti-angiogenic therapy as soon as 1 day after bevacizumab-based therapy. The addition of MRS to conventional MR methods can provide better insight into how anti-angiogenic therapy affects tumor microenvironment and predict patient outcomes.

Background Patients with recurrent glioblastoma (GBM) are often treated with antiangiogenic agents, such as bevacizumab (BEV). Despite therapeutic promise, conventional MRI methods fail to help determine which patients may not benefit from this treatment. Purpose To use MR spectroscopic imaging (MRSI) with intermediate and short echo time to measure corrected myo-inositol (mI)normalized by contralateral creatine (hereafter, mI/c-Cr) in participants with recurrent GBM treated with BEV and to investigate whether such measurements can help predict survivorship before BEV initiation (baseline) and at 1 day, 4 weeks, and 8 weeks thereafter. Materials and Methods In this prospective longitudinal study (2016-2020), spectroscopic data on mI-a glial marker and osmoregulator within the brain-normalized by contralateral creatine in the intratumoral, contralateral, and peritumoral volumes of patients with recurrent GBM were evaluated. Area under the receiver operating characteristic curve (AUC) was calculated for all volumes at baseline and 1 day, 4 weeks, and 8 weeks after treatment to determine the ability of mI/c-Cr to help predict survivorship. Results Twenty-one participants (median age ± standard deviation, 62 years ± 12; 15 men) were evaluated. Lower mI/c-Cr in the tumor before and during BEV treatment was predictive of poor survivorship, with receiver operating characteristic analyses showing an AUC of 0.75 at baseline, 0.87 at 1 day after treatment, and 1 at 8 weeks after. A similar result was observed in contralateral normal-appearing tissue and the peritumoral volume, with shorter-term survivors having lower levels of mI/c-Cr. In the contralateral volume, a lower ratio of mI to creatine (hereafter, mI/Cr) predicted shorter-term survival at baseline and all other time points. Within the peritumoral volume, lower mI/c-Cr levels were predictive of shorter-term survival at baseline (AUC, 0.80), at 1 day after treatment (AUC, 0.93), and at 4 weeks after treatment (AUC, 0.68). Conclusion Lower levels of myo-inositol normalized by contralateral creatine within intratumoral, contralateral, and peritumoral volumes were predictive of poor survivorship and antiangiogenic treatment failure as early as before bevacizumab treatment. Adapting MR spectroscopic imaging alongside conventional MRI modalities conveys critical information regarding the biologic characteristics of tumors to help better treat individuals with recurrent glioblastoma. Clinical trial registration no. NCT02843230 © RSNA, 2021 Online supplemental material is available for this article.

Adults use distributed cues in the bodies of others to predict and counter their actions. To investigate the development of this ability, we had adults and 6- to 8-year-old children play a competitive game with a confederate who reached toward one of two targets. Child and adult participants, who sat across from the confederate, attempted to beat the confederate to the target by touching it before the confederate did. Adults used cues distributed through the head, shoulders, torso, and arms to predict the reaching actions. Children, in contrast, used cues in the arms and torso, but we did not find any evidence that they could use cues in the head or shoulders to predict the actions. These results provide evidence for a change in the ability to respond rapidly to predictive cues to others' actions from childhood to adulthood. Despite humans' sensitivity to action goals even in infancy, the ability to read cues from the body for action prediction in rapid interactive settings is still developing in children as old as 6 to 8 years of age.

Purpose Reduced stress commonly occurs in talkers with Parkinson's disease (PD), whereas excessive and equal stress is frequently associated with dysarthria of talkers with amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). This study sought to identify articulatory impairment patterns that underlie these two impaired stress patterns. We further aimed to determine if talkers with the same stress pattern disturbance but different diseases (ALS and MS) exhibit disease-specific articulatory deficits. Method Fifty-seven talkers participated in the study—33 talkers with dysarthria and 24 controls. Talkers with dysarthria were grouped based on their medical diagnosis: PD (n = 15), ALS (n = 10), MS (n = 8). Participants repeated target words embedded in a carrier phrase. Kinematic data were recorded using electromagnetic articulography. Duration, displacement, peak speed, stiffness, time-to-peak speed, and parameter c were extracted for the initial lower lip opening stroke of each target word, which was either stressed or unstressed. Results Stress effects were significant for all kinematic measures across groups except for stiffness and time-to-peak speed, which were nonsignificant in ALS. For comparisons with controls, more kinematic measures significantly differed in the ALS group than in the PD and MS groups. Additionally, ALS and MS showed mostly similar articulatory impairment patterns. Conclusions In general, significant stress effects were observed in talkers with dysarthria. However, stress-specific between-group differences in articulatory performance, particularly displacement, may explain the perceptual impression of disturbed stress patterns. Furthermore, similar findings for ALS and MS suggest that articulatory deficits underlying similar stress pattern disturbances are not disease-specific.

Patients with recurrent glioblastoma (rGBM) are often started on anti-angiogenic therapy such as bevacizumab. However, determining treatment failure using conventional MRI methods remains challenging. We prospectively collected longitudinal MR spectroscopy data in 33 patients with rGBM and quantified various metabolites including N-acetylaspartate (NAA), Choline (Cho), and Lactate (Lac). After stratifying patients by 9 month survival, we found that longer-term survivors had decreased Lac/NAA and increased NAA/Cho compared to shorter-term survivors. ROC analyses illustrated that intratumoral changes in NAA/Cho were predictive of survival at 1 day (AUC 0.92), 2 weeks (AUC 0.75), 8 weeks (AUC 0.71) and 16 weeks (AUC 0.85) but not 4 weeks (AUC 0.60). Intratumoral changes in Lac/NAA were predictive of survival at all time points tested (AUCs > 0.76 for all time points). At 8 weeks, 90% of patients with increased Lac/NAA from baseline and 88% of patients with decreased NAA/Cho did not survive 9 months. Changes in NAA/Cho and Lac/NAA may serve as early biomarkers of anti-angiogenic treatment failure.

In our recent study (Diehl et al., 2019), we examined the perceptual speech features of 48 talkers with Huntington's disease (HD) using the classic feature-based dysarthria rating scale (Darley et al., 1969). A cluster analysis based on speech feature ratings revealed four dysarthria subgroups within our cohort of talkers with HD. Talkers within each subgroup shared deviant speech features that set them apart from talkers with HD in other subgroups. Presumably, talkers with similar patterns of deviant speech features sound alike. In the current study, we will test this notion using a free classification approach. Specifically, 20 naïve listeners will be asked to sort the speech samples of 48 talkers with HD that were used in the previous study into similar-sounding groups. Each listener's grouping decision will be submitted to an additive similarity tree cluster analysis to determine dysarthria subgroups based on the free classification task. Moreover, subgroup-specific speech features will be determined based on the previously established perceptual ratings of the classic dysarthria rating scale. Study outcomes will provide insights into the saliency of specific perceptual speech features in talkers with HD.

Adults use distributed cues in the bodies of others to predict and counter their actions. To investigate the development of this ability, adults and 6-to 8-year-old children played a competitive game with a confederate who reached toward one of two targets. Child and adult participants, who sat across from the confederate, attempted to beat the confederate to the target by touching it before the confederate did. Adults used cues distributed through the head, shoulders, and body to predict the reaching actions. Children, in contrast, used cues in the arms and torso but not in the head, face or shoulders to predict the actions. These results provide evidence for a qualitative change in the ability to respond rapidly to predictive cues to others’ actions develops slowly over childhood. Despite children’s sensitivity to eye gaze even in infancy, cues from the head and body do not influence their action predictions as late as 8 years of age.

A multi-center imaging trial by the American College of Radiology Imaging Network (ACRIN) “A Multicenter, phase II assessment of tumor hypoxia in glioblastoma using 18F Fluoromisonidazole (FMISO) with PET and MRI (ACRIN 6684)”, was conducted to assess hypoxia in patients with glioblastoma (GBM). The aims of this study were to support the role of proton magnetic resonance spectroscopic imaging (1H MRSI) as a prognostic marker for brain tumor patients in multi-center clinical trials. Seventeen participants from four sites had analyzable 3D MRSI datasets acquired on Philips, GE or Siemens scanners at either 1.5T or 3T. MRSI data were analyzed using LCModel to quantify metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lactate (Lac). Receiver operating characteristic curves for NAA/Cho, Cho/Cr, lactate/Cr, and lactate/NAA were constructed for overall survival at 1-year (OS-1) and 6-month progression free survival (PFS-6). The OS-1 for the 17 evaluable patients was 59% (10/17). Receiver operating characteristic analyses found the NAA/Cho in tumor (AUC = 0.83, 95% CI: 0.61 to 1.00) and in peritumoral regions (AUC = 0.95, 95% CI 0.85 to 1.00) were predictive for survival at 1 year. PFS-6 was 65% (11/17). Neither NAA/Cho nor Cho/Cr was effective in predicting 6-month progression free survival. Lac/Cr in tumor was a significant negative predictor of PFS-6, indicating that higher lactate/Cr levels are associated with poorer outcome. (AUC = 0.79, 95% CI: 0.54 to 1.00). In conclusion, despite the small sample size in the setting of a multi-center trial comprising different vendors, field strengths, and varying levels of expertise at data acquisition, MRS markers NAA/Cho, Lac/Cr and Lac/NAA predicted overall survival at 1 year and 6-month progression free survival. This study validates that MRSI may be useful in evaluating the prognosis in glioblastoma and should be considered for incorporating into multi-center clinical trials.

We investigate with experiments and computer simulations the nonequilibrium dynamics of DNA polymers crossing arrays of entropic barriers in nanofluidic devices in a pressure-driven flow. With increasing driving pressure, the effective diffusivity of DNA rises and then peaks at a value that is many times higher than the equilibrium diffusivity. This is an entropic manifestation of "giant acceleration of diffusion." The phenomenon is sensitive to the effective energy landscape; thus, it offers a unique probe of entropic barriers in a system driven away from equilibrium.

We designed a two-person competitive reaching task in a naturalistic setting to compare the action reading ability of 6–8-year-old children and adults. Two participants faced each other separated by a Plexiglass screen. One (a confederate adult Attacker) was instructed to touch one of two targets on the screen, and the other (a child or an adult Blocker) was told to touch the same target as quickly as possible. In both children and adults, Blocker reaction times were fast, much faster than the reaction times to a dot projected on the screen moving in the same manner. These results suggest that Blockers use subtle preparatory movements of Attackers to predict their goal. Next, we occluded body parts of the Attacker to determine the location of the bodily cues used by adults and children to achieve fast reactions. Both children and adults reacted fast when only the torso and arms were visible. Adults also reacted fast when only the head and shoulders were visible, indicating that they were able to read the goal of the Attacker from the cues in the head and shoulders, but children did not. These results suggest that adult humans have knowledge of the biomechanical constraints of the bodily movements of others and use it to accurately predict actions. This ability is present but still developing in 6–8- year-old children.

OBJECTIVESDuring hospitalizations, blood is drawn for diagnostic laboratory tests to help guide patient care. Often, blood tests continue to be ordered even in the face of clinical and laboratory stability. Blood draws are painful and costly, and they may be associated with anemia. We hypothesized that provider education could reduce the frequency of daily blood tests ordered for hospitalized patients.METHODSDuring a 2-month intervention period, internal medicine providers were educated through flyers displayed in providers' offices and periodic email communications reminding them to order daily blood tests only if the results would change patient care. Two-month preintervention data from 982 patients and 2-month postintervention data from 988 patients were analyzed. The primary outcome measured was the number of daily blood tests ordered per patient per day.RESULTSMean orders of CBC decreased from 1.46 to 1.37 tests per patient per day (P < .05) after the intervention. Basic metabolic panel orders were reduced from 0.91 to 0.83 tests per patient per day (P < .05). Cost analyses showed a reduction of $6.33 per patient day based on the decrease in the number of daily laboratory tests ordered.CONCLUSIONSProvider education and reminders can reduce the frequency of daily blood tests ordered by providers for hospitalized patients. This can decrease health care costs and may reduce the risk of complications such as anemia.

Traditionally, collagen mimetic peptides (CMPs) have been used for elucidating the structure of the collagen triple helix and the factors responsible for its stabilization. The wealth of fundamental knowledge on collagen structure and cell-extracellular matrix (ECM) interactions accumulated over the past decades has led to a recent burst of research exploring the potential of CMPs to recreate the higher order assembly and biological function of natural collagens for biomedical applications. Although a large portion of such research is still at an early stage, the collagen triple helix has become a promising structural motif for engineering self-assembled, hierarchical constructs similar to natural tissue scaffolds which are expected to exhibit unique or enhanced biological activities. This paper reviews recent progress in the field of collagen mimetic peptides that bears both direct and indirect implications to engineering collagen-like materials for potential biomedical use. Various CMPs and collagen-like proteins that mimic either structural or functional characteristics of natural collagens are discussed with particular emphasis on providing helpful information to bioengineers and biomaterials scientists interested in collagen engineering.

+variations within the hip, we imaged an oil phantom of known T1 (~550 ms), with the B1 + scale of the saturation pulse manually adjusted from 0.8-1.2 (0.05 steps) of its nominally calibrated B1