Agents targeting prostate-specific membrane antigen (PSMA) comprise a rapidly emerging class of radiopharmaceuticals for diagnostic imaging of prostate cancer. Unlike most other PSMA agents with a ...urea backbone, CTT1057 is based on a phosphoramidate scaffold that irreversibly binds to PSMA. We conducted a first-in-humans phase I study of CTT1057 in patients with localized and metastatic prostate cancer. Methods: Two patient cohorts were recruited. Cohort A patients had biopsy-proven localized prostate cancer preceding radical prostatectomy, and cohort B patients had metastatic castration-resistant prostate cancer. Cohort A patients were imaged at multiple time points after intravenous injection with 362 ± 8 MBq of CTT1057 to evaluate the kinetics of CTT1057 and estimate radiation dose profiles. Mean organ-absorbed doses and effective doses were calculated. CTT1057 uptake in the prostate gland and regional lymph nodes was correlated with pathology, PSMA staining, and the results of conventional imaging. In cohort B, patients were imaged 60–120 min after injection of CTT1057. PET images were assessed for overall image quality, and areas of abnormal uptake were contrasted with conventional imaging. Results: In cohort A (n = 5), the average total effective dose was 0.023 mSv/MBq. The kidneys exhibited the highest absorbed dose, 0.067 mGy/MBq. The absorbed dose of the salivary glands was 0.015 mGy/MBq. For cohort B (n = 15), CTT1057 PET detected 97 metastatic lesions, and 44 of 56 bone metastases detected on CTT1057 PET (78.5%) were also detectable on bone scanning. Eight of 32 lymph nodes positive on CTT1057 PET (25%) were enlarged by size criteria on CT. Conclusion: CTT1057 is a promising novel phosphoramidate PSMA-targeting 18F-labeled PET radiopharmaceutical that demonstrates similar biodistribution to urea-based PSMA-targeted agents, with lower exposure to the kidneys and salivary glands. Metastatic lesions are detected with higher sensitivity on CTT1057 imaging than on conventional imaging. Further prospective studies with CTT1057 are warranted to elucidate its role in cancer imaging.
The majority of pediatric emergency patients are seen in mixed-age emergency departments and triaged by general emergency nurses. Educational methods for teaching pediatric triage education to ...general emergency nurses have not been well studied, and previous studies of the use of the Emergency Severity Index in children have been performed primarily in centers that are high volume for pediatrics.
A repeated-measures, randomized crossover study comparing 2 different methods of pediatric triage education was conducted. Participants were general emergency nurses recruited from a general emergency department that is classified as low volume for pediatrics. Each participant was exposed in a random order to both educational methods: paper-based cases and high-fidelity simulation.
All participants had substantial improvement in pediatric triage accuracy as measured by a standardized set of pediatric triage cases. The previously reported trend toward undertriage of the pediatric patient was observed despite a mean triage agreement rate of 73% at the end of the study period. No differences were observed between groups; the order of the educational intervention did not result in statistically significant differences in triage accuracy.
A combined approach of paper-based cases and high-fidelity simulation was effective at improving pediatric triage accuracy among a group of general ED nurses with limited exposure to pediatric patients. The results from this study suggest that combining both methods of education may be a viable means of providing general emergency nurses with additional knowledge in pediatric triage; however, persistent trends in undertriage should be studied further.
Intermediate-risk prostate cancer is a heterogeneous disease state with diverse treatment options. The 22-gene Decipher genomic classifier (GC) retrospectively has shown to improve risk ...stratification in these patients. We assessed the performance of the GC in men with intermediate-risk disease enrolled in NRG Oncology/RTOG 01-26 with updated follow-up.
After National Cancer Institute approval, biopsy slides were collected from NRG Oncology/RTOG 01-26, a randomized phase 3 trial of men with intermediate-risk prostate cancer randomized to 70.2 Gy versus 79.2 Gy of radiation therapy without androgen deprivation therapy. RNA was extracted from the highest-grade tumor foci to generate the locked 22-gene GC model. The primary endpoint for this ancillary project was disease progression (composite of biochemical failure, local failure, distant metastasis, prostate cancer-specific mortality, and use of salvage therapy). Individual endpoints were also assessed. Fine-Gray or cause-specific Cox multivariable models were constructed adjusting for randomization arm and trial stratification factors.
Two-hundred fifteen patient samples passed quality control for analysis. The median follow-up was 12.8 years (range, 2.4-17.7). On multivariable analysis, the 22-gene GC (per 0.1 unit) was independently prognostic for disease progression (subdistribution hazard ratio sHR, 1.12; 95% confidence interval CI, 1.00-1.26; P = .04), biochemical failure (sHR, 1.22; 95% CI, 1.10-1.37; P < .001), distant metastasis (sHR, 1.28; 95% CI, 1.06-1.55; P = .01), and prostate cancer-specific mortality (sHR, 1.45; 95% CI, 1.20-1.76; P < .001). Ten-year distant metastasis in GC low-risk patients was 4% compared with 16% for GC high-risk patients. In patients with lower GC scores, the 10-year difference in metastasis-free survival rate between arms was -7%, compared with 21% for higher GC patients (P-interaction = .04).
This study represents the first validation of a biopsy-based gene expression classifier, assessing both its prognostic and predictive value, using data from a randomized phase 3 trial of intermediate-risk prostate cancer. Decipher improves risk stratification and can aid in treatment decision-making in men with intermediate-risk disease.
Low health literacy in older adults has been associated with poor health outcomes (i.e., mortality, decreased physical and cognitive functioning, and less preventive care utilization). Many factors ...associated with low health literacy are also associated with health disparities. Interaction with healthcare providers and sources of health information are influenced by an individual's health literacy and can impact health outcomes.
This study examined the relationships between health literacy, sources of health information, and demographic/background characteristics in older adults (aged 65 years and older) related to health literacy and disparities.
This descriptive, correlational study is a secondary analysis of the 2003 National Assessment of Adult Literacy, a large-scale national assessment.
Older adults with lower health literacy have less income and education, rate their health as poor or fair, have visual or auditory difficulties, need help filling out forms, reading newspaper, or writing notes, and use each source of health information less (print and nonprint). Many of these characteristics and skills are predictive of health literacy and associated with health disparities.
The results expand our knowledge of characteristics associated with health literacy and sources of health information used by older adults. Interventions to improve health outcomes including health disparities can focus on recognizing and meeting the health literacy demands of older adults.
Deep understanding of genetic architecture of water-stress tolerance is critical for efficient and optimal development of water-stress tolerant cultivars, which is the most economical and ...environmentally sound approach to maintain lettuce production with limited irrigation. Lettuce (
L.) production in areas with limited precipitation relies heavily on the use of ground water for irrigation. Lettuce plants are highly susceptible to water-stress, which also affects their nutrient uptake efficiency. Water stressed plants show reduced growth, lower biomass, and early bolting and flowering resulting in bitter flavors. Traditional phenotyping methods to evaluate water-stress are labor intensive, time-consuming and prone to errors. High throughput phenotyping platforms using kinetic chlorophyll fluorescence and hyperspectral imaging can effectively attain physiological traits related to photosynthesis and secondary metabolites that can enhance breeding efficiency for water-stress tolerance. Kinetic chlorophyll fluorescence and hyperspectral imaging along with traditional horticultural traits identified genomic loci affected by water-stress. Supervised machine learning models were evaluated for their accuracy to distinguish water-stressed plants and to identify the most important water-stress related parameters in lettuce. Random Forest (RF) had classification accuracy of 89.7% using kinetic chlorophyll fluorescence parameters and Neural Network (NN) had classification accuracy of 89.8% using hyperspectral imaging derived vegetation indices. The top ten chlorophyll fluorescence parameters and vegetation indices selected by sequential forward selection by RF and NN were genetically mapped using a
×
interspecific recombinant inbred line (RIL) population. A total of 25 quantitative trait loci (QTL) segregating for water-stress related horticultural traits, 26 QTL for the chlorophyll fluorescence traits and 34 QTL for spectral vegetation indices (VI) were identified. The percent phenotypic variation (PV) explained by the horticultural QTL ranged from 6.41 to 19.5%, PV explained by chlorophyll fluorescence QTL ranged from 6.93 to 13.26% while the PV explained by the VI QTL ranged from 7.2 to 17.19%. Eight QTL clusters harboring co-localized QTL for horticultural traits, chlorophyll fluorescence parameters and VI were identified on six lettuce chromosomes. Molecular markers linked to the mapped QTL clusters can be targeted for marker-assisted selection to develop water-stress tolerant lettuce.
Ivabradine, the selective inhibitor of the If current in the sinoatrial node, exerts cardiovascular protection by its bradycardic effect and potentially pleiotropic actions. However, there is a ...shortage of data regarding ivabradine's interaction with the renin-angiotensin-aldosterone system (RAAS). This study investigated whether ivabradine is able to protect a hypertensive heart in the model of
-NAME-induced hypertension and to interfere with the RAAS. Four groups (
= 10/group) of adult male Wistar rats were treated as follows for four weeks: control, ivabradine (10 mg/kg/day),
-NAME (40 mg/kg/day), and
-NAME plus ivabradine.
-NAME administration increased systolic blood pressure (SBP) and left ventricular (LV) weight, enhanced hydroxyproline concentration in the LV, and deteriorated the systolic and diastolic LV function. Ivabradine reduced heart rate (HR) and SBP, and improved the LV function. The serum concentrations of angiotensin Ang 1⁻8 (Ang II), Ang 1⁻5, Ang 1⁻7, Ang 1⁻10, Ang 2⁻8, and Ang 3⁻8 were decreased in the
-NAME group and ivabradine did not modify them. The serum concentration of aldosterone and the aldosterone/Ang II ratio were enhanced by
-NAME and ivabradine reduced these changes. We conclude that ivabradine improved the LV function of the hypertensive heart in
-NAME-induced hypertension. The protective effect of ivabradine might have been associated with the reduction of the aldosterone level.
Decipher is a genomic classifier (GC) prospectively validated postprostatectomy. We validated the performance of the GC in pretreatment biopsy samples within the context of 3 randomized phase 3 ...high-risk definitive radiation therapy trials.
A prespecified analysis plan (NRG-GU-TS006) was approved to obtain formalin-fixed paraffin-embedded tissue from biopsy specimens from the NRG biobank from patients enrolled in the NRG/Radiation Therapy Oncology Group (RTOG) 9202, 9413, and 9902 phase 3 randomized trials. After central review, the highest-grade tumors were profiled on clinical-grade whole-transcriptome arrays and GC scores were obtained. The primary objective was to validate the independent prognostic ability for the GC for distant metastases (DM), and secondary for prostate cancer–specific mortality (PCSM) and overall survival (OS) with Cox univariable and multivariable analyses.
GC scores were obtained on 385 samples, of which 265 passed microarray quality control (69%) and had a median follow-up of 11 years (interquartile range, 9-13). In the pooled cohort, on univariable analysis, the GC was shown to be a prognostic factor for DM (per 0.1 unit; subdistribution hazard ratio sHR, 1.29; 95% confidence interval CI, 1.18-1.41; P < .001), PCSM (sHR, 1.28; 95% CI, 1.16-1.41; P < .001), and OS (hazard ratio HR, 1.16; 95% CI, 1.08-1.22; P < .001). On multivariable analyses, the GC (per 0.1 unit) was independently associated with DM (sHR, 1.22; 95% CI, 1.09-1.36), PCSM (sHR, 1.23; 95% CI, 1.09-1.39), and OS (HR, 1.12; 95% CI, 1.05-1.20) after adjusting for age, Prostate Specific Antigen, Gleason score, cT stage, trial, and randomized treatment arm. GC had similar prognostic ability in patients receiving short-term or long-term androgen-deprivation therapy, but the absolute improvement in outcome varied by GC risk.
This is the first validation of a gene expression biomarker on pretreatment prostate cancer biopsy samples from prospective randomized trials and demonstrates an independent association of GC score with DM, PCSM, and OS. High-risk prostate cancer is a heterogeneous disease state, and GC can improve risk stratification to help personalize shared decision making.
Innovative mechanical services coupled with renewable energy systems are crucial for achieving a net zero energy goal for houses. Conventional systems tend to be vastly oversized because they lack ...the means to buffer energy flows and are based on peak loads. This paper presents an approach to achieve a net zero energy goal for houses by using a solar PV system, heat pumps, and thermal and electrical storage batteries, all off-the-shelf. Constraining one part of the system and then showing how to manage energy storage and flow is a paradigm shift in sizing. The design is for a modest-sized house built in Melbourne, Australia. The output of a solar photovoltaic array drives a small-scale heat pump to heat water, buffering its energy in a thermal battery to energise a radiant space heating system. Space cooling is provided by a separate heat pump. Through energy storage in electrical and thermal batteries, it is possible to meet the electricity, heating and cooling needs of the house for the Melbourne climate with a heat pump that draws less than 1 kW. The design methodology is detailed in an appendix and can be applied to similar projects. This paper contributes to similar work worldwide that aims to reinforce innovative renewable energy driven service design.
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