Sharing FAIR monitoring program data improves discoverability and reuse.

Data resulting from environmental monitoring programs are valuable assets for natural resource managers, decision-makers, and researchers. These data are often collected to inform specific reporting needs or decisions with a specific timeframe. While program-oriented data and related publications are effective for meeting program goals, sharing well-documented data and metadata allows users to research aspects outside initial program intentions. As part of an effort to integrate data from four long-term large-scale US aquatic monitoring programs, we evaluated the original datasets against the FAIR (Findable, Accessible, Interoperable, Reusable) data principles and offer recommendations and lessons learned. Differences in data governance across these programs resulted in considerable effort to access and reuse the original datasets. Requirements, guidance, and resources available to support data publishing and documentation are inconsistent across agencies and monitoring programs, resulting in various data formats and storage locations that are not easily found, accessed, or reused. Making monitoring data FAIR will reduce barriers to data discovery and reuse. Programs are continuously striving to improve data management, data products, and metadata; however, provision of related tools, consistent guidelines and standards, and more resources to do this work is needed. Given the value of these data and the significant effort required to access and reuse them, actions and steps intended on improving data documentation and accessibility are described.

Validity of physical activity measures in individuals after total knee arthroplasty.

OBJECTIVE: To determine the concurrent criterion-related validity of 2 activity monitors in comparison with the criterion method of indirect calorimetry in older adults after total knee arthroplasty (TKA). DESIGN: Validation study. SETTING: Subjects completed 9 increasingly demanding daily activities in a research laboratory; each activity was performed for 7 minutes, for a total of 80 minutes, while the activity monitors and criterion method were used concurrently. PARTICIPANTS: Subjects (N=21, 67% women) had a mean age ± SD of 68±7 years and a body mass index of 29±4. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Energy expenditure (in kcal/min) measured by accelerometer-based and multisensor-based monitors and by a criterion method. Validity was assessed by the paired t test, intraclass correlation coefficient (ICC), and Bland-Altman plots comparing the measurements from the activity monitors with those of the criterion method. RESULTS: Measurements from the accelerometer-based monitor were significantly lower than those of the criterion method across all walking and nonwalking activities. The underestimations ranged from 40% to 100%. The accelerometer-based monitor demonstrated small to moderate agreement compared with the criterion method (ICCs from 0 to .38). Measurements from the multisensor-based monitor were significantly lower than those of the criterion method during several nonwalking activities; yet, the differences were minor (2%-19%). Measurements from the multisensor-based monitor during walking activities were not different compared with the criterion method. The multisensor-based monitor demonstrated moderate to excellent agreement with the criterion method (ICCs from .48 to .81). CONCLUSIONS: The multisensor-based monitor showed better criterion-related validity than the accelerometer-based monitor and should be considered as a tool to measure physical activity in individuals after TKA.

Improving motor control in walking: a randomized clinical trial in older adults with subclinical walking difficulty.

OBJECTIVE: To test the proposed mechanism of action of a task-specific motor learning intervention by examining its effect on measures of the motor control of gait. DESIGN: Single-blinded randomized clinical trial. SETTING: University research laboratory. PARTICIPANTS: Adults (N=40) aged ≥65 years with gait speed >1.0m/s and impaired motor skill (figure-of-8 walk time >8s). INTERVENTIONS: The 2 interventions included a task-oriented motor learning and a standard exercise program; both interventions included strength training. Both lasted 12 weeks, with twice-weekly, 1-hour, physical therapist-supervised sessions. MAIN OUTCOME MEASURES: Two measures of the motor control of gait, gait variability and smoothness of walking, were assessed pre- and postintervention by assessors masked to the treatment arm. RESULTS: Of 40 randomized subjects, 38 completed the trial (mean age ± SD, 77.1±6.0y). The motor learning group improved more than the standard group in double-support time variability (.13m/s vs .05m/s; adjusted difference [AD]=.006, P=.03). Smoothness of walking in the anteroposterior direction improved more in the motor learning than standard group for all conditions (usual: AD=.53, P=.05; narrow: AD=.56, P=.01; dual task: AD=.57, P=.04). Smoothness of walking in the vertical direction also improved more in the motor learning than standard group for the narrow-path (AD=.71, P=.01) and dual-task (AD=.89, P=.01) conditions. CONCLUSIONS: Among older adults with subclinical walking difficulty, there is initial evidence that task-oriented motor learning exercise results in gains in the motor control of walking, while standard exercise does not. Task-oriented motor learning exercise is a promising intervention for improving timing and coordination deficits related to mobility difficulties in older adults, and needs to be evaluated in a definitive larger trial.

The Test-Retest Reliability of Indirect Calorimetry Measures of Energy Expenditure During Overground Walking in Older Adults With Mobility Limitations.

The purpose of this study was to assess the relative and absolute reliability of metabolic measures of energy expenditure and gait speed during overground walking in older adults with mobility limitations. Thirty-three (mean age [SD] = 76.4 [6.6] years; 66% female) older adults with slow gait participated. Measures of energy expenditure and gait speed were recorded during two 6-min bouts of overground walking (1 week apart) at a self-selected "usual" walking pace. The relative reliability for all variables was excellent: ICC = .81-.91. Mean differences for five of the six outcome variables was less than or equal to the respected SEM, while all six mean differences fell below the calculated MDC95. Clinicians and researchers can be confident that metabolic measures of energy expenditure and gait speed in older adults with slow walking speeds can be reliably assessed during overground walking, providing an alternative to traditional treadmill assessments.

What is the relation between fear of falling and physical activity in older adults?

OBJECTIVE: To describe the association between fear of falling (FOF) and total daily activity in older adults. DESIGN: Cross-sectional observational study. SETTING: Ambulatory clinical research training center. PARTICIPANTS: Community-dwelling older adults aged ≥64 years (N=78), who were independent in ambulation with or without an assistive device. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: FOF was defined by self-reported fear ratings using the Survey of Activities and Fear of Falling in the Elderly and self-reported fear status determined by response to the following question: Are you afraid of falling? Physical function was assessed using the Late Life Function and Disability Instrument. Physical activity was recorded using an accelerometer worn on the waist for 7 consecutive days, and mean daily counts of activity per minute were averaged over the 7-day period. RESULTS: Fear ratings were related to total daily activity (r=-.26, P=.02). The relation was not as strong as the relation of function and physical activity (r=.45, P<.001). When stratified by exercise status or functional status, fear was no longer related to total daily activity. Physical function explained 19% of the variance in physical activity, whereas the addition of fear status did not add to the explained variance in physical activity. CONCLUSIONS: FOF is related to total daily physical activity; however, FOF was not independently associated with physical activity when accounting for physical function. Some FOF may be reported as a limitation in function.

Prostate stem cell antigen is an endogenous lynx1-like prototoxin that antagonizes alpha7-containing nicotinic receptors and prevents programmed cell death of parasympathetic neurons.

Vertebrate alpha-bungarotoxin-like molecules of the Ly-6 superfamily have been implicated as balancers of activity and survival in the adult nervous system. To determine whether a member of this family could be involved in the development of the avian ciliary ganglion, we identified 6 Gallus genes by their homology in structure to mouse lynx1 and lynx2. One of these genes, an ortholog of prostate stem cell antigen (psca), is barely detectable at embryonic day (E) 8, before neuronal cell loss in the ciliary ganglion, but increases >100-fold as the number of neurons begins to decline between E9 and E14. PSCA is highly expressed in chicken and mouse telencephalon and peripheral ganglia and correlates with expression of alpha7-containing nicotinic acetylcholine receptors (alpha7-nAChRs). Misexpressing PSCA before cell death in the ciliary ganglion blocks alpha7-nAChR activation by nicotine and rescues the choroid subpopulation from dying. Thus, PSCA, a molecule previously identified as a marker of prostate cancer, is a member of the Ly-6 neurotoxin-like family in the nervous system, and is likely to play a role as a modulator of alpha7 signaling-induced cell death during development.

Characteristics of walking, activity, fear of falling, and falls in community-dwelling older adults by residence.

OBJECTIVES: Research focusing on community-dwelling older adults includes adults living in senior living residences (SLR) and independent community residences (ICR). Walking, physical activity, fear of falling, and fall history may differ on the basis of residence. PURPOSE: We describe characteristics of walking, physical activity, fear of falling, and fall history between community-dwelling older adults by residence. METHODS: Participants of this secondary analysis included community-dwelling older adults from independent living units within a senior life care community (SLR) and older adults recruited from the Pittsburgh community (ICR). Demographic information and physical (gait speed and physical activity), psychosocial (fear of falling and confidence in walking), and fall history measures were collected. RESULTS: Adults living in SLR compared with those in ICR were older, were more likely to live alone, and had greater disease burden. Compared with individuals in ICR, individuals in SLR reported less fear of falling (Survey of Activity and Fear of Falling in the Elderly tool fear results 0.24 and 0.50, respectively). Fewer older adults in SLR compared with those in ICR reported falling in the past year. DISCUSSION: Older adults living in SLR compared with those in ICR had similar physical function but differed in report of fear of falling and fall history. Recognizing the possible differences in psychosocial function by place of residence is important for health care providers and researchers conducting interventions and studies for community-dwelling older adults.

Intraclass Correlation Coefficients for Planning Cluster Randomized Trials in Community-Dwelling Older Adults.

Objectives: With the emerging trends, more cluster randomized trials will be conducted in older adults, where facilities are randomized rather than individuals. Similarity of individuals from a facility (intraclass correlation coefficient/ICC) plays a critical role, but not readily available. We document ICCs for measures commonly used in community-dwelling older adults and discuss implications. Method: Secondary analysis of a range of baseline measures from the On the Move cluster randomized trial, whose ICCs were computed using a linear mixed model. Results: Self-reported disability measures related to facility characteristics and sense of community had the greatest ICCs (>0.10), while mobility performance measures had 0.05 to 0.10, and cognitive measure 0.11. Discussion: The ICCs for measures commonly used in older adults are of a sufficient magnitude to have a substantial impact on planned sample size of a study and credibility of results, and should be taken into consideration in study planning and data analysis.

Exercise-Based Interventions to Enhance Long-Term Sustainability of Physical Activity in Older Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Exercise is a form of physical activity (PA). PA is an important marker of health and quality of life in older adults. The purpose of this study was to conduct a systematic review of the literature to assess the effect of exercise-based interventions on an at least six-month follow up PA measure, and to describe the specific strategies implemented during the intervention to strengthen the sustainability of PA in community-dwelling 65+ year-old adults. We registered and conducted a systematic review and meta-analysis (PROSPERO: CRD42017070892) of randomized clinical trials (RCT). We searched three electronic databases during January 2018 to identify RCT assessing any type of exercise-based intervention. Studies had to report a pre-, post-, and at least 6-month post-intervention follow-up. To be included, at least one PA outcome had to be assessed. The effect of exercise-based interventions was assessed compared to active (e.g., a low-intensity type of exercise, such as stretching or toning activities) and non-active (e.g., usual care) control interventions at several time points. Secondary analyses were conducted, restricted to studies that reported specific strategies to enhance the sustainability of PA. The intervention effect was measured on self-reported and objective measures of time spent in PA, by means of standardized mean differences. Standardized mean differences of PA level were pooled. Pooled estimates of effect were computed with the DerSimonian-Laird method, applying a random effects model. The risk of bias was also assessed. We included 12 studies, comparing 18 exercise intervention groups to four active and nine non-active control groups. Nine studies reported specific strategies to enhance the long-term sustainability of PA. The strategies were mostly related to the self-efficacy, self-control, and behavior capability principles based on the social cognitive theory. Exercise interventions compared to active control showed inconclusive and heterogeneous results. When compared to non-active control, exercise interventions improved PA time at the six-months follow up (standardized mean difference (SMD) 0.30; 95%CI 0.15 to 0.44; four studies; 724 participants; I2 0%), but not at the one- or two-years follow-ups. No data were available on the mid- and long-term effect of adding strategies to enhance the sustainability of PA. Exercise interventions have small clinical benefits on PA levels in community-dwelling older adults, with a decline in the observed improvement after six months of the intervention cessation.

Motor Control-based Group Exercise: Can It be Delivered as Effectively by Lay Leaders?

PURPOSE: On the Move (OTM), a motor control-based group exercise program for community-dwelling older adults, has produced greater gains in mobility than a standard group exercise program when delivered by research leaders. The purposes of this study were:1) to examine the effectiveness of OTM versus a standard program when delivered by lay leaders and 2) to compare the outcomes of OTM when delivered by research versus lay leaders. METHODS: Community-dwelling, medically stable older adults who could walk household distances participated. OTM consisted of warm-up, timing and coordination, strengthening, and stretching exercises. The seated standard program consisted of warm-up, aerobic, strengthening and stretching exercises. The primary outcome(s) of function and disability was the Late Life Function and Disability Instrument (LLFDI), and for walking ability were the Six Minute Walk Test and gait speed. RESULTS: 126 participants (mean age = 80.7±7.8 years, gait speed = 0.91 m/s) were randomized to OTM (n=49) or standard (n=77) programs. When taught by lay leaders, there were no significant between-intervention group differences in any of the outcomes (p>0.10). Comparing OTM outcomes between leaders, there was a statistical but not clinically meaningful difference in LLFDI disability (1.87±0.89, p=0.04) when taught by research versus lay leader, and moderate differences (p=0.06) in LLFDI overall function (1.89±1.02) and gait speed (0.05±0.03). Qualitative interview responses suggest that instructor-related concerns may have impacted program outcomes. CONCLUSION: When delivered by lay leaders OTM was not more effective than a standard program for improving function, disability, and mobility in older adults. Health promotion programs designed to improve mobility in community-dwelling older adults and based on a motor control theoretical background, may be best taught by rehabilitation professionals.

The oligomeric structure of high molecular weight adiponectin.

There is great interest in the structure of adiponectin as its oligomeric state may specify its biological activities. It occurs as a trimer, a hexamer and a high molecular weight complex. Epidemiological data indicate that the high molecular weight form is significant with low serum levels in type 2 diabetics but to date, has not been well-defined. To resolve this issue, characterization of this oligomer from bovine serum and 3T3-L1 adipocytes by sedimentation equilibrium centrifugation and gel electrophoresis respectively, was carried out, revealing that it is octadecameric. Further studies by dynamic light scattering and electron microscopy established that bovine and possibly mouse high molecular weight adiponectin is C1q-like in structure.

EphrinA1-Fc attenuates myocardial ischemia/reperfusion injury in mice.

EphrinA1, a membrane-bound receptor tyrosine kinase ligand expressed in healthy cardiomyocytes, is lost in injured cells following myocardial infarction. Previously, we have reported that a single intramyocardial injection of chimeric ephrinA1-Fc at the time of ischemia reduced injury in the nonreperfused myocardium by 50% at 4 days post-MI by reducing apoptosis and inflammatory cell infiltration. In a clinically relevant model of acute ischemia (30min)/reperfusion (24hr or 4 days) injury, we now demonstrate that ephrinA1-Fc reduces infarct size by 46% and completely preserves cardiac function (ejection fraction, fractional shortening, and chamber dimensions) in the short-term (24hrs post-MI) as well as long-term (4 days). At 24 hours post-MI, diminished serum inflammatory cell chemoattractants in ephrinA1-Fc-treated mice reduces recruitment of neutrophils and leukocytes into the myocardium. Differences in relative expression levels of EphA-Rs are described in the context of their putative role in mediating cardioprotection. Validation by Western blotting of selected targets from mass spectrometry analyses of pooled samples of left ventricular tissue homogenates from mice that underwent 30min ischemia and 24hr of reperfusion (I/R) indicates that ephrinA1-Fc administration alters several regulators of signaling pathways that attenuate apoptosis, promote autophagy, and shift from FA metabolism in favor of increased glycolysis to optimize anaerobic ATP production. Taken together, reduced injury is due a combination of adaptive metabolic reprogramming, improved cell survival, and decreased inflammatory cell recruitment, suggesting that ephrinA1-Fc enhances the capacity of the heart to withstand an ischemic insult.

The Impact of a Portable Metabolic Measurement Device on Gait Characteristics of Older Adults With Mobility Limitations.

BACKGROUND AND PURPOSE: Increased carriage loads have been found to alter gait biomechanics in young healthy adults and military personnel; however, less is known regarding the influence of added carriage load on the gait characteristics of older adults-especially those with mobility limitations. The purpose of this study was to examine spatial and temporal gait characteristics during instrumented and noninstrumented overground walking in a sample of older adults with slow gait. METHODS: Forty older adults with slow gait completed 2 bouts of walking (instrumented and noninstrumented) over a computerized walkway during 1 clinic visit. Mean spatial-temporal characteristics, gait variability, and gait speed over 8 passes were recorded. Paired t tests and intraclass correlation coefficients were used to quantify differences. RESULTS AND DISCUSSION: Nine of the 10 gait variables did not differ statistically between instrumented and noninstrumented gait (P < .05). Intraclass correlation coefficients (ICCs) for mean gait characteristics were excellent (range ICC = 0.94-0.98; 95% confidence interval = 0.89-0.99), and for gait variability ranged from fair to excellent (range ICC = 0.56-0.79; 95% confidence interval = 0.28-0.89). Our study was able to demonstrate no significant impact of instrumentation on gait characteristics in a sample of older adults with slow gait. CONCLUSION: Our findings begin to fill in the gaps in the literature regarding the impact of added carriage loads on more vulnerable populations and lend support for the use of similar weighted metabolic devices as a component of gait assessment in older adults with confidence that the additional carriage-load will not significantly impact concurrent measures of gait.

Voluntary exercise improves hypothalamic and metabolic function in obese mice.

Exercise plays a critical role in regulating glucose homeostasis and body weight. However, the mechanism of exercise on metabolic functions associated with the CNS has not been fully understood. C57BL6 male mice (n=45) were divided into three groups: normal chow diet, high-fat diet (HFD) treatment, and HFD along with voluntary running wheel exercise training for 12 weeks. Metabolic function was examined by the Comprehensive Lab Animal Monitoring System and magnetic resonance imaging; phenotypic analysis included measurements of body weight, food intake, glucose and insulin tolerance tests, as well as insulin and leptin sensitivity studies. By immunohistochemistry, the amount changes in the phosphorylation of signal transducer and activator of transcription 3, neuronal proliferative maker Ki67, apoptosis positive cells as well as pro-opiomelanocortin (POMC)-expressing neurons in the arcuate area of the hypothalamus was identified. We found that 12 weeks of voluntary exercise training partially reduced body weight gain and adiposity induced by an HFD. Insulin and leptin sensitivity were enhanced in the exercise training group verses the HFD group. Furthermore, the HFD-impaired POMC-expressing neuron is remarkably restored in the exercise training group. The restoration of POMC neuron number may be due to neuroprotective effects of exercise on POMC neurons, as evidenced by altered proliferation and apoptosis. In conclusion, our data suggest that voluntary exercise training improves metabolic symptoms induced by HFD, in part through protected POMC-expressing neuron from HFD and enhanced leptin signaling in the hypothalamus that regulates whole-body energy homeostasis.

Stakeholder involvement in the design of a patient-centered comparative effectiveness trial of the "On the Move" group exercise program in community-dwelling older adults.

BACKGROUND: Group exercise programs for older adults often exclude the timing and coordination of movement. Stakeholder involvement in the research process is strongly encouraged and improves the relevance and adoption of findings. We describe stakeholder involvement in the design of a clinical trial of a group-based exercise program that incorporates timing and coordination of movement into the exercises. METHODS: The study was a cluster randomized, single-blind intervention trial to compare the effects on function, disability and mobility of a standard group exercise program and the "On the Move" group exercise program in older adults residing in independent living facilities and senior apartment buildings, and attending community centers. Exercise classes were twice weekly for 12weeks delivered by study exercise leaders and facility activity staff personnel. OUTCOMES: The primary outcomes function, disability and mobility were assessed at baseline and post-intervention. Function and disability were assessed using the Late Life Function and Disability Instrument, and mobility using the Six-Minute Walk Test and gait speed. STAKEHOLDERS: Patient and provider stakeholders had significant input into the study aims, design, sample, intervention, outcomes and operational considerations. SUMMARY: A community-based exercise program to improve walking can be developed to address both investigator identified missing components in current exercise to improve walking and stakeholder defined needs and interest for the activity program. Involvement of stakeholders substantially improves the relevance of research questions, increases the transparency of research activities and may accelerate the adoption of research into practice.

The association between energy cost of walking and physical function in older adults.

To assess the association between energy cost of walking and self-report of function, independent of comorbidity and gait speed, in older adults with mobility limitations. This cross-sectional observational study was conducted within an ambulatory clinical research training center. Forty-two older adults, age 65 and older, with slow and variable gait participated. Function was assessed using the Late Life Function and Disability Index-Basic Lower Extremity Subscale, while energy cost of walking was derived by standardizing the mean oxygen consumption recorded during physiological steady state by gait speed. Comorbidity and gait speed were collected as co-variates. Pearson's r correlation coefficient and regression analyses were used to assess the relationship between energy cost and function. Energy cost of walking was significantly correlated with self-reported function (Pearson's r=-0.50, p<0.001); furthermore, energy cost of walking explained an additional 17% (p=0.002) of the variance in self-reported function above and beyond the variance explained by comorbidity and gait speed combined. Energy cost of walking is emerging as another significant factor related to functional performance among older adults, even after controlling for comorbidity and gait speed - robust variables known for their strong contributions to function. Knowledge of and attention to the efficiency of how one moves (high energy cost of walking) may enhance rehabilitation efforts to further reduce "functional burden" in older adults.

Motor learning versus standard walking exercise in older adults with subclinical gait dysfunction: a randomized clinical trial.

OBJECTIVES: To compare the effect of motor learning with that of standard exercise on measures of mobility and perceived function and disability. DESIGN: Single-blind randomized trial. SETTING: University research center. PARTICIPANTS: Older adults (n = 40) with a mean age of 77.1 ± 6.0, normal walking speed (≥ 1.0 m/s), and impaired motor skills (Figure of 8 walk time >8 seconds). INTERVENTIONS: The motor learning program incorporated goal-oriented stepping and walking to promote timing and coordination within the phases of the gait cycle. The standard program employed endurance training by treadmill walking. Both included strength training and were offered twice weekly for 1 hour for 12 weeks. MEASUREMENTS: Primary outcomes were mobility performance (gait efficiency, motor skill in walking, gait speed, walking endurance); secondary outcomes were perceived function and disability (Late-Life Function and Disability Instrument). RESULTS: Thirty-eight of 40 participants completed the trial (motor learning, n = 18; standard, n = 20). The motor learning group improved more than the standard group in gait speed (0.13 vs 0.05 m/s, P = .008) and motor skill (-2.2 vs -0.89 seconds, P < .001). Both groups improved in walking endurance (28.3 and 22.9 m, P = .14). Changes in gait efficiency and perceived function and disability were not different between the groups (P > .10). CONCLUSION: In older adults with subclinical gait dysfunction, motor learning exercise improved some parameters of mobility performance more than standard exercise.

Serial diffusion MRI to monitor and model treatment response of the targeted nanotherapy CRLX101.

PURPOSE: Targeted nanotherapies are being developed to improve tumor drug delivery and enhance therapeutic response. Techniques that can predict response will facilitate clinical translation and may help define optimal treatment strategies. We evaluated the efficacy of diffusion-weighted magnetic resonance imaging to monitor early response to CRLX101 (a cyclodextrin-based polymer particle containing the DNA topoisomerase I inhibitor camptothecin) nanotherapy (formerly IT-101), and explored its potential as a therapeutic response predictor using a mechanistic model of tumor cell proliferation. EXPERIMENTAL DESIGN: Diffusion MRI was serially conducted following CRLX101 administration in a mouse lymphoma model. Apparent diffusion coefficients (ADCs) extracted from the data were used as treatment response biomarkers. Animals treated with irinotecan (CPT-11) and saline were imaged for comparison. ADC data were also input into a mathematical model of tumor growth. Histological analysis using cleaved-caspase 3, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, Ki-67, and hematoxylin and eosin (H&E) were conducted on tumor samples for correlation with imaging results. RESULTS: CRLX101-treated tumors at day 2, 4, and 7 posttreatment exhibited changes in mean ADC = 16 ± 9%, 24 ± 10%, 49 ± 17%, and size (TV) = -5 ± 3%, -30 ± 4%, and -45 ± 13%, respectively. Both parameters were statistically greater than controls [p(ADC) ≤ 0.02, and p(TV) ≤ 0.01 at day 4 and 7], and noticeably greater than CPT-11-treated tumors (ADC = 5 ± 5%, 14 ± 7%, and 18 ± 6%; TV = -15 ± 5%, -22 ± 13%, and -26 ± 8%). Model-derived parameters for cell proliferation obtained using ADC data distinguished CRLX101-treated tumors from controls (P = 0.02). CONCLUSIONS: Temporal changes in ADC specified early CRLX101 treatment response and could be used to model image-derived cell proliferation rates following treatment. Comparisons of targeted and nontargeted treatments highlight the utility of noninvasive imaging and modeling to evaluate, monitor, and predict responses to targeted nanotherapeutics.

Pathogenesis of human hemangiosarcomas and hemangiomas.

Hemangiosarcomas are uncommon aggressive vascular tumors that have recently become the focus of attention because several chemicals and pharmaceuticals increase their incidence in mice. The relevance of these mouse vascular tumors to humans is unclear. In the present study, we semiquantitatively evaluated the expression profiles of hematopoietic stem cell markers (CD117 [c-kit], CD133, CD34, and CD45), endothelial cell markers (vascular endothelial growth factor receptor 2, CD31, and factor VIII-related antigen), and a myeloid lineage cell marker (CD14) in human hemangiosarcoma (n = 12) and hemangioma (n = 10) specimens using immunohistochemistry. CD133 was completely negative in almost all cases of hemangiosarcomas and hemangiomas. Most hemangiosarcomas, but not hemangiomas, stained for CD117 and CD45. Both groups diffusely expressed CD34, vascular endothelial growth factor receptor 2, and factor VIII-related antigen; however, hemangiomas had more intense and diffuse CD34 and factor VIII-related antigen expression compared with hemangiosarcomas, whereas CD31 was positive in all hemangiosarcomas but only half of the hemangiomas. CD14 staining was negative in most hemangiosarcoma and hemangioma cases. Our results indicate that multipotential bone marrow-derived hematopoietic stem cells or early endothelial progenitor cells (EPCs) expressing CD117, CD34, and CD45 are involved in hemangiosarcoma formation, whereas hemangiomas originate from late EPCs or differentiated endothelial cells, which have lost the expression of most hematopoietic stem cell markers. This contrasts with our previous results that demonstrated that both hemangiosarcomas and hemangiomas in mice may be derived from early EPCs that are not completely differentiated.

Perceived effort of walking: relationship with gait, physical function and activity, fear of falling, and confidence in walking in older adults with mobility limitations.

BACKGROUND: Although clinicians have a number of measures to use to describe walking performance, few, if any, of the measures capture a person's perceived effort in walking. Perceived effort of walking may be a factor in what a person does versus what he or she is able to do. OBJECTIVE: The objective of this study was to examine the relationship of perceived effort of walking with gait, function, activity, fear of falling, and confidence in walking in older adults with mobility limitations. Design This investigation was a cross-sectional, descriptive, relational study. METHODS: The study took place at a clinical research training center. The participants were 50 older adults (mean age=76.8 years, SD=5.5) with mobility limitations. The measurements used were the Rating of Perceived Exertion (RPE) for walking; gait speed; the Modified Gait Abnormality Rating Scale; energy cost of walking; Late Life Function and Disability Instrument (LLFDI) for total, basic, and advanced lower-extremity function and for disability limitations; activity and restriction subscales of the Survey of Activities and Fear of Falling in the Elderly (SAFFE); activity counts; SAFFE fear subscale; and Gait Efficacy Scale (GES). The relationship of the RPE of walking with gait, function, activity, fear, and confidence was determined by using Spearman rank order coefficients and an analysis of variance (adjusted for age and sex) for mean differences between groups defined by no exertion during walking and some exertion during walking. RESULTS: The RPE was related to confidence in walking (GES, R=-.326, P=.021) and activity (activity counts, R=.295, P=.044). The RPE groups (no exertion versus some exertion) differed in LLFDI scores for total (57.9 versus 53.2), basic (68.6 versus 61.4), and advanced (49.1 versus 42.6) lower-extremity function; LLFDI scores for disability limitations (74.9 versus 67.5); SAFFE fear subscale scores (0.346 versus 0.643); and GES scores (80.1 versus 67.8) (all P<.05). Limitations The range of RPE scores for the participants studied was narrow. Thus, the real correlations between RPE and gait, physical function, and psychological aspects of walking may be greater than the relationships reported. CONCLUSIONS: The perceived effort of walking was associated with physical activity and confidence in walking. Reducing the perceived effort of walking may be an important target of interventions to slow the decline in function of older adults with mobility limitations.