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BACKGROUND: Assessment of individual tumor biology and response to systemic therapy in pancreatic ductal adenocarcinoma (PDAC) remains a clinical challenge. The significance of anthropometric (body composition) changes during chemotherapy as a surrogate for tumor biology in the setting of localized PDAC is unknown. METHODS: A retrospective, single-institution analysis of patients with PDAC who received neoadjuvant therapy (NAT) and pancreatectomy from 2017 to 2021 was performed. Radiologic anthropometric analysis used artificial intelligence-driven software to segment and compute total and sub-compartment muscle area, adipose tissue area, and attenuation values at the level of the L3 vertebra. Kaplan-Meier survival estimates, log-rank tests, and multivariable Cox regression models were used in survival analyses. RESULTS: The inclusion criteria were met by 138 patients. Although decreases in muscle and adipose tissue areas during NAT were predominant, a subset of patients experienced an increase in these compartments. Increases in muscle greater than 5% (hazard ratio [HR], 0.352; 95% confidence interval [CI] 0.135-0.918; p = 0.033) and increases in adipose tissue greater than 15% (HR, 0.375; 95% CI 0.144-0.978; p = 0.045), were significantly associated with improved survival, whereas loss of visceral fat greater than 15% was detrimental (HR 1.853; CI 1.099-3.124; p = 0.021). No significant associations with single time-point anthropometrics were observed. Gains in total muscle and adipose mass were associated with improved pathologic response to systemic therapy and less advanced pathologic tumor stage. CONCLUSIONS: Dynamic anthropometric analysis during NAT for PDAC is a stronger prognostic indicator than measurements taken at a single point in time. Repeated anthropometric analysis during preoperative chemotherapy may serve as a biomarker for individual tumor biology and response to therapy.
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OBJECTIVES: The listening demand incurred by speech perception fluctuates in normal conversation. At the acoustic-phonetic level, natural variation in pronunciation acts as speedbumps to accurate lexical selection. Any given utterance may be more or less phonetically ambiguous-a problem that must be resolved by the listener to choose the correct word. This becomes especially apparent when considering two common speech registers-clear and casual-that have characteristically different levels of phonetic ambiguity. Clear speech prioritizes intelligibility through hyperarticulation which results in less ambiguity at the phonetic level, while casual speech tends to have a more collapsed acoustic space. We hypothesized that listeners would invest greater cognitive resources while listening to casual speech to resolve the increased amount of phonetic ambiguity, as compared with clear speech. To this end, we used pupillometry as an online measure of listening effort during perception of clear and casual continuous speech in two background conditions: quiet and noise. DESIGN: Forty-eight participants performed a probe detection task while listening to spoken, nonsensical sentences (masked and unmasked) while recording pupil size. Pupil size was modeled using growth curve analysis to capture the dynamics of the pupil response as the sentence unfolded. RESULTS: Pupil size during listening was sensitive to the presence of noise and speech register (clear/casual). Unsurprisingly, listeners had overall larger pupil dilations during speech perception in noise, replicating earlier work. The pupil dilation pattern for clear and casual sentences was considerably more complex. Pupil dilation during clear speech trials was slightly larger than for casual speech, across quiet and noisy backgrounds. CONCLUSIONS: We suggest that listener motivation could explain the larger pupil dilations to clearly spoken speech. We propose that, bounded by the context of this task, listeners devoted more resources to perceiving the speech signal with the greatest acoustic/phonetic fidelity. Further, we unexpectedly found systematic differences in pupil dilation preceding the onset of the spoken sentences. Together, these data demonstrate that the pupillary system is not merely reactive but also adaptive-sensitive to both task structure and listener motivation to maximize accurate perception in a limited resource system.
Subject(s)
Pupil , Speech Perception , Humans , Pupil/physiology , Speech , Noise , Cognition , Speech Perception/physiology , Speech Intelligibility/physiologyABSTRACT
Development interventions increasingly include women's empowerment and gender equality among their objectives, but evaluating their impact has been stymied by the lack of measures that are comparable across interventions. This paper synthesizes the findings of 11 mixed-methods impact evaluations of agricultural development projects from South Asia and sub-Saharan Africa that were part of the Gender, Agriculture, and Assets Project, Phase 2 (GAAP2). As part of GAAP2, qualitative and quantitative data were used to develop and validate the multidimensional project-level Women's Empowerment in Agriculture Index (pro-WEAI), which was used to assess the impact of GAAP2 projects on women's empowerment. This paper assesses the extent to which: (1) a two- to three-year agricultural development project can contribute to women's empowerment; and (2) a suite of methods comprising a standardized quantitative measure of women's empowerment and a set of qualitative protocols, can evaluate such impacts. Our synthesis finds that the most common positive significant impacts were on the instrumental and collective agency indicators that comprise pro-WEAI, owing to the group-based approaches used. We found few projects significantly improved intrinsic agency, even among those with explicitly stated objectives to change gender norms. Unsurprisingly, we find mixed, and mostly null impacts on aggregate pro-WEAI, with positive impacts more likely in the South Asian, rather than African, cases. Our results highlight the need for projects to design their strategies specifically for empowerment, rather than assume that projects aiming to reach and benefit women automatically empower them. Our study also shows the value of a suite of methods containing a common metric to compare empowerment impacts and qualitative protocols to understand and contextualize these impacts.
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OBJECTIVES: To examine the association between tinnitus and hearing outcomes among US military personnel after blast injury, including any hearing loss, low-frequency hearing loss, high-frequency hearing loss, early warning shift, and significant threshold shift. DESIGN: In this retrospective study, the Blast-Related Auditory Injury Database was queried for male military service members who had audiometric data 2 years before and after blast injury between 2004 and 2012 with no history of hearing loss or tinnitus before injury (n = 1693). Tinnitus was defined by diagnostic codes in electronic health records. Multivariable logistic regression examined the association between tinnitus and hearing outcomes, while adjusting for covariates. RESULTS: Overall, 14.2% (n = 241) of the study sample was diagnosed with tinnitus within 2 years after blast injury. The proportions of all examined hearing outcomes were higher among service members with tinnitus than those without ( p < 0.001). In multivariable analysis, service members with tinnitus had higher adjusted odds of any hearing loss (odds ratio [OR] = 1.72, 95% confidence interval [CI] = 1.20-2.47), low-frequency hearing loss (OR = 2.77, 95% CI = 1.80-4.26), high-frequency hearing loss (OR = 2.15, 95% CI = 1.47-3.16), early warning shift (OR = 1.83, 95% CI = 1.36-2.45), and significant threshold shift (OR = 2.15, 95% CI = 1.60-2.89) compared with service members without tinnitus. CONCLUSIONS: The findings of this study demonstrate that tinnitus diagnosed within 2 years after blast injury is associated with the examined hearing outcomes in US military personnel. Service members with blast injury who subsequently experience tinnitus should receive routine audiometric hearing conservation testing and be carefully examined for poor hearing outcomes by an audiologist.
Subject(s)
Blast Injuries , Deafness , Hearing Loss , Military Personnel , Tinnitus , Humans , Male , Tinnitus/epidemiology , Tinnitus/complications , Blast Injuries/complications , Blast Injuries/epidemiology , Retrospective Studies , Hearing , Hearing Loss/epidemiology , Hearing Loss/complications , Deafness/complicationsABSTRACT
INTRODUCTION: Pediatric asthma exacerbations are a common cause of emergency medical services (EMS) encounters. Bronchodilators and systemic corticosteroids are mainstays of asthma exacerbation therapy, yet data on the efficacy of EMS administration of systemic corticosteroids are mixed. This study's objective was to assess the association between EMS administration of systemic corticosteroids to pediatric asthma patients on hospital admission rates based on asthma exacerbation severity and EMS transport intervals. METHODS: This is a sub-analysis of the Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial (EASI AS ODT). EASI AS ODT is a non-randomized, stepped wedge, observational study examining outcomes one year before and one year after seven EMS agencies incorporated an oral systemic corticosteroid option into their protocols for the treatment of pediatric asthma exacerbations. We included EMS encounters for patients ages 2-18 years confirmed by manual chart review to have asthma exacerbations. We compared hospital admission rates across asthma exacerbation severities and EMS transport intervals using univariate analyses. We geocoded patients and created maps to visualize the general trends of patient characteristics. RESULTS: A total of 841 pediatric asthma patients met inclusion criteria. While most patients were administered inhaled bronchodilators by EMS (82.3%), only 21% received systemic corticosteroids, and only 19% received both inhaled bronchodilators and systemic corticosteroids. Overall, there was no significant difference in hospitalization rates between patients who did and did not receive systemic corticosteroids from EMS (33% vs. 32%, p = 0.78). However, although not statistically significant, for patients who received systemic corticosteroids from EMS, there was an 11% decrease in hospitalizations for mild exacerbation patients and a 16% decrease in hospitalizations for patients with EMS transport intervals greater than 40 min. CONCLUSION: In this study, systemic corticosteroids were not associated with a decrease in hospitalizations of pediatric patients with asthma overall. However, while limited by small sample size and lack of statistical significance, our results suggest there may be a benefit in certain subgroups, particularly patients with mild exacerbations and those with transport intervals longer than 40 min. Given the heterogeneity of EMS agencies, EMS agencies should consider local operational and pediatric patient characteristics when developing standard operating protocols for pediatric asthma.
Subject(s)
Anti-Asthmatic Agents , Asthma , Emergency Medical Services , Humans , Child , Bronchodilator Agents/therapeutic use , Anti-Asthmatic Agents/therapeutic use , Administration, Inhalation , Asthma/drug therapy , Adrenal Cortex Hormones/therapeutic useABSTRACT
BACKGROUND: The National Football League (NFL) and National Football League Players Association implemented a set of strict protocols for the 2020 season with the intent to mitigate COVID-19 risk among players and staff. In that timeframe, the league's 32 teams completed 256 regular season games and several thousand meetings and practices. In parallel, community cases of COVID-19 were highly prevalent. We assess the risk of holding a 2020 NFL season by comparing community and player COVID-19 infections. METHODS: We used county-level COVID-19 test data from each team to establish baseline distributions of infection rates expected to occur in a population similar in age and sex to NFL players. We used a binomial distribution to simulate expected infections in each community cohort and compared these findings with observed COVID-19 infections in players. RESULTS: Over a 5-month period (1 August 2020 to 2 January 2021), positive NFL player infections (n = 256) were 55.7% lower than expected when compared with simulations from NFL community cohorts. For 30 of 32 teams (94%), observed counts fell at or below expectation, including 28 teams (88%) for which rates were lower. Two teams fell above baseline expectation. CONCLUSIONS: The NFL/NFLPA protocols that governed team facilities, travel, gameday, and activities outside of the workplace were associated with lower infection rates among NFL players compared with the surrounding community. The NFL's 2020-2021 season are consistent with the hypothesis that robust testing and behavioral protocols support a safe return to sport and work.
Subject(s)
COVID-19 , Football , Cohort Studies , Humans , SARS-CoV-2 , SeasonsABSTRACT
Federally Qualified Health Centers (FQHCs) are organizations that provide primary care services to our nation's most vulnerable communities. This nurse practitioner-led intervention sought to double the number of available COVID-19 evaluation and testing appointments within an FQHC. Results showed a significant increase in the availability of respiratory clinic appointments, the number of completed appointments, and the number of tests completed. This demonstrates nurse practitioners' ability to work with organizations to develop innovative systems that can be adapted for future use. (Am J Public Health. 2022;112(S3):S284-S287. https://doi.org/10.2105/AJPH.2022.306827).
Subject(s)
COVID-19 , Ambulatory Care Facilities , Appointments and Schedules , COVID-19/diagnosis , COVID-19/epidemiology , Health Services Accessibility , HumansABSTRACT
During December 2021, the United States experienced a surge in COVID-19 cases, coinciding with predominance of the SARS-CoV-2 B.1.1.529 (Omicron) variant (1). During this surge, the National Football League (NFL) and NFL Players Association (NFLPA) adjusted their protocols for test-to-release from COVID-19 isolation on December 16, 2021, based on analytic assessments of their 2021 test-to-release data. Fully vaccinated* persons with COVID-19 were permitted to return to work once they were asymptomatic or fever-free and experiencing improving symptoms for ≥24 hours, and after two negative or high cycle-threshold (Ct) results (Ct≥35) from either of two reverse transcription-polymerase chain reaction (RT-PCR) tests (2). This report describes data from NFL's SARS-CoV-2 testing program (3) and time to first negative or Ct≥35 result based on serial COVID-19 patient testing during isolation. Among this occupational cohort of 173 fully vaccinated adults with confirmed COVID-19 during December 14-19, 2021, a period of Omicron variant predominance, 46% received negative test results or had a subsequent RT-PCR test result with a Ct≥35 by day 6 postdiagnosis (i.e., concluding 5 days of isolation) and 84% before day 10. The proportion of persons with positive test results decreased with time, with approximately one half receiving positive RT-PCR test results after postdiagnosis day 5. Although this test result does not necessarily mean these persons are infectious (RT-PCR tests might continue to return positive results long after an initial positive result) (4), these findings indicate that persons with COVID-19 should continue taking precautions, including correct and consistent mask use, for a full 10 days after symptom onset or initial positive test result if they are asymptomatic.
Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Quarantine , Return to Sport , Return to Work , SARS-CoV-2 , Adult , Athletes , COVID-19/prevention & control , Football , Humans , Male , United States/epidemiologyABSTRACT
BACKGROUND: Rapid COVID-19 testing platforms can identify infected individuals at the point of care (POC), allowing immediate isolation of infected individuals and reducing the risk of transmission. While lab-based nucleic acid amplification testing (NAAT) is often considered the gold standard to detect SARS-CoV-2 in the community, results typically take 2-7 days to return, rendering POC testing a critical diagnostic tool for infection control. The National Football League (NFL) and NFL Players Association deployed a new POC testing strategy using a newly available reverse transcriptase polymerase chain reaction (RT-PCR) rapid test during the 2020 season, and evaluated diagnostic effectiveness compared to other available devices using real-world population surveillance data. METHODS: RT-PCR POC test results were compared to NAAT results from same-day samples by calculation of positive and negative concordance. Sensitivity analyses were performed for three subgroups: (1) individuals symptomatic at time of positive test; (2) individuals tested during the pilot phase of rollout; and (3) individuals tested daily. RESULTS: Among 4989 same-day POC/NAAT pairs, 4957 (99.4%) were concordant, with 93.1% positive concordance and 99.6% negative concordance. Based on adjudicated case status, the false negative rate was 0.2% and false positive rate was 2.9%. In 43 instances, the immediate turnaround of results by POC allowed isolation of infected individuals 1 day sooner than lab-based testing. Positive/negative concordance in sensitivity analyses were relatively stable. CONCLUSION: RT-PCR POC testing provided timely results that were highly concordant with lab-based NAAT in population surveillance. Expanded use of effective RT-PCR POC can enable rapid isolation of infected individuals and reduce COVID-19 infection in the community.
Subject(s)
COVID-19 , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Testing , Humans , Point-of-Care Testing , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , Sensitivity and SpecificityABSTRACT
OBJECTIVE: To evaluate relationships between specific cerebellar regions and common clinical measures of motor and cognitive function in persons with multiple sclerosis (PwMS). DESIGN: Cross-sectional. SETTING: Laboratory. PARTICIPANTS: Twenty-nine PwMS and 28 age- and sex-matched controls without multiple sclerosis (MS) (N=57). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Both diffusion and lobule magnetic resonance imaging analyses and common clinical measures of motor and cognitive function were used to examine structure-function relationships in the cerebellum. RESULTS: PwMS demonstrate significantly worse motor and cognitive function than controls, including weaker strength, slower walking, and poorer performance on the Symbol Digit Modalities Test, but demonstrate no differences in cerebellar volume. However, PwMS demonstrate significantly worse diffusivity (mean diffusivity: P=.0003; axial diffusivity: P=.0015; radial diffusivity: P=.0005; fractional anisotropy: P=.016) of the superior cerebellar peduncle, the primary output of the cerebellum. Increased volume of the motor lobules (I-V, VIII) was significantly related to better motor (P<.022) and cognitive (P=.046) performance, and increased volume of the cognitive lobules (VI-VII) was also related to better motor (P<.032) and cognitive (P=.008) performance, supporting the role of the cerebellum in both motor and cognitive functioning. CONCLUSIONS: These data highlight the contributions of the cerebellum to both motor and cognitive function in PwMS. Using novel neuroimaging techniques to examine structure-function relationships in PwMS improves our understanding of individualized differences in this heterogeneous group and may provide an avenue for targeted, individualized rehabilitation aimed at improving cerebellar dysfunction in MS.
Subject(s)
Multiple Sclerosis , Cerebellum/diagnostic imaging , Cognition , Cross-Sectional Studies , Humans , Magnetic Resonance Imaging , Multiple Sclerosis/diagnostic imagingABSTRACT
BACKGROUND: Evidence to understand effective strategies for surveillance and early detection of SARS-CoV-2 is limited. OBJECTIVE: To describe the results of a rigorous, large-scale COVID-19 testing and monitoring program. DESIGN: The U.S. National Football League (NFL) and the NFL Players Association (NFLPA) instituted a large-scale COVID-19 monitoring program involving daily testing using 2 reverse transcription polymerase chain reaction (RT-PCR) platforms (Roche cobas and Thermo Fisher QuantStudio), a transcription-mediated amplification platform (Hologic Panther), and an antigen point-of-care (aPOC) test (Quidel Sofia). SETTING: 32 NFL clubs in 24 states during the 2020 NFL season. PARTICIPANTS: NFL players and staff. MEASUREMENTS: SARS-CoV-2 test results were described in the context of medically adjudicated status. Cycle threshold (Ct) values are reported when available. RESULTS: A total of 632 370 tests administered across 11 668 persons identified 270 (2.4%) COVID-19 cases from 1 August to 14 November 2020. Positive predictive values ranged from 73.0% to 82.0% across the RT-PCR platforms. High Ct values (33 to 37) often indicated early infection. For the first positive result, the median Ct value was 32.77 (interquartile range, 30.02 to 34.72) and 22% of Ct values were above 35. Among adjudicated COVID-19 cases tested with aPOC, 42.3% had a negative result. Positive concordance between aPOC test result and adjudicated case status increased as viral load increased. LIMITATIONS: Platforms varied by laboratory, and test variability may reflect procedural differences. CONCLUSION: Routine RT-PCR testing allowed early detection of infection. Cycle threshold values provided a useful guidepost for understanding results, with high values often indicating early infection. Antigen POC testing was unable to reliably rule out COVID-19 early in infection. PRIMARY FUNDING SOURCE: The NFL and the NFLPA.
Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , COVID-19/diagnosis , Football , Occupational Health , COVID-19/epidemiology , Early Diagnosis , Humans , Incidence , SARS-CoV-2 , United States/epidemiologyABSTRACT
Parkinson's disease (PD) is a neurodegenerative condition primarily associated with its motor consequences. Although much of the focus within the speech domain has focused on PD's consequences for production, people with PD have been shown to differ in the perception of emotional prosody, loudness, and speech rate from age-matched controls. The current study targeted the effect of PD on perceptual phonetic plasticity, defined as the ability to learn and adjust to novel phonetic input, both in second language and native language contexts. People with PD were compared to age-matched controls (and, for three of the studies, a younger control population) in tasks of explicit non-native speech learning and adaptation to variation in native speech (compressed rate, accent, and the use of timing information within a sentence to parse ambiguities). The participants with PD showed significantly worse performance on the task of compressed rate and used the duration of an ambiguous fricative to segment speech to a lesser degree than age-matched controls, indicating impaired speech perceptual abilities. Exploratory comparisons also showed people with PD who were on medication performed significantly worse than their peers off medication on those two tasks and the task of explicit non-native learning.
Subject(s)
Parkinson Disease , Speech Perception , Humans , Language , Phonetics , SpeechABSTRACT
ABSTRACT: Incorporation of interprofessional activities within health profession programs is critical to prepare students for practice. Faculty at our institution saw a need to incorporate interprofessional education in the nursing, pharmacy, social work, and dietetics program curricula. We collaborated with a medical school in the area to develop a mobile, community-based interprofessional clinic to deliver care and education and address the needs of older adults while also providing unique, meaningful learning opportunities for students. We describe several lessons learned from our experience of developing and implementing this interprofessional clinic.
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The National Football League (NFL) and the NFL Players Association (NFLPA) began the 2020 football season in July, implementing extensive mitigation and surveillance measures in facilities and during travel and gameplay. Mitigation protocols* were evaluated and modified based on data from routine reverse transcription-polymerase chain reaction (RT-PCR) tests for SARS-CoV-2, the virus that causes coronavirus 2019 (COVID-19); proximity tracking devices; and detailed interviews. Midseason, transmission was observed in persons who had cumulative interactions of <15 minutes' duration, leading to a revised definition of high-risk contacts that required consideration of mask use, setting and room ventilation in addition to proximity and duration of interaction. The NFL also developed an intensive protocol that imposed stricter infection prevention precautions when a case was identified at an NFL club. The intensive protocol effectively prevented the occurrence of high-risk interactions, with no high-risk contacts identified for 71% of traced cases at clubs under the intensive protocol. The incorporation of the nature and location of the interaction, including mask use, indoor versus outdoor setting, and ventilation, in addition to proximity and duration, likely improved identification of exposed persons at higher risk for SARS-CoV-2 infection. Quarantine of these persons, along with testing and intensive protocols, can reduce spread of infection.
Subject(s)
COVID-19 Testing , COVID-19/prevention & control , Contact Tracing , Football , COVID-19/epidemiology , COVID-19/transmission , Humans , Masks/statistics & numerical data , Physical Distancing , Quarantine/statistics & numerical data , Risk Assessment , SARS-CoV-2/isolation & purification , Time Factors , United States/epidemiology , Ventilation/statistics & numerical dataABSTRACT
Expectations regarding gendered behaviors are understood to emanate from many sources, including parents, peers, and the self but there has been little research directly comparing these three sources of pressure. The present study assessed felt pressure regarding masculine and feminine stereotypic behaviors and compared pressure from parents, peers, and the self and how these sources are associated with self-perceived gender typicality. Participants (N = 275; 53.09% female; grade 7 M = 12.35 years; grade 9 M = 14.3 years; 71% Anglo-Celtic) were recruited from independent schools in Sydney. Felt pressure from the self to engage in masculine behavior was greater than felt pressure from parents or peers. Male adolescents reported higher felt pressure to conform to gender conforming behavior from parents and the self and pressure to avoid gender nonconforming behavior was greatest from peers. Female adolescents reported felt pressure to conform to gender nonconforming behaviors and this pressure was the strongest from the self. Additionally, for both genders, felt pressure from the self was most consistently associated with gender typicality. These findings highlight the importance of self-expectations for gender cognitions relating to both masculine and feminine behaviors.
Subject(s)
Gender Identity , Peer Group , Adolescent , Emotions , Female , Humans , Male , Parents , Social BehaviorABSTRACT
A listener's interpretation of a given speech sound can vary probabilistically from moment to moment. Previous experience (i.e., the contexts in which one has encountered an ambiguous sound) can further influence the interpretation of speech, a phenomenon known as perceptual learning for speech. This study used multivoxel pattern analysis to query how neural patterns reflect perceptual learning, leveraging archival fMRI data from a lexically guided perceptual learning study conducted by Myers and Mesite [Myers, E. B., & Mesite, L. M. Neural systems underlying perceptual adjustment to non-standard speech tokens. Journal of Memory and Language, 76, 80-93, 2014]. In that study, participants first heard ambiguous /s/-/∫/ blends in either /s/-biased lexical contexts (epi_ode) or /∫/-biased contexts (refre_ing); subsequently, they performed a phonetic categorization task on tokens from an /asi/-/a∫i/ continuum. In the current work, a classifier was trained to distinguish between phonetic categorization trials in which participants heard unambiguous productions of /s/ and those in which they heard unambiguous productions of /∫/. The classifier was able to generalize this training to ambiguous tokens from the middle of the continuum on the basis of individual participants' trial-by-trial perception. We take these findings as evidence that perceptual learning for speech involves neural recalibration, such that the pattern of activation approximates the perceived category. Exploratory analyses showed that left parietal regions (supramarginal and angular gyri) and right temporal regions (superior, middle, and transverse temporal gyri) were most informative for categorization. Overall, our results inform an understanding of how moment-to-moment variability in speech perception is encoded in the brain.
Subject(s)
Speech Perception , Speech , Humans , Language , Learning , PhoneticsABSTRACT
OBJECTIVES: To develop a transcriptomic signature capable of predicting overall survival (OS) for uterine serous carcinoma (USC). METHODS: RNAseq data for 58 USC patients were obtained from TCGA. Expression of 73 candidate genes was measured for 67 Augusta University (AU) samples using NanoString technology. RESULTS: Analysis of the TCGA RNAseq data identified 73 genes that individually predict prognosis for USC patients and an elastic net model with all 73 genes (USC73) distinguishes a good OS group with low USC73 score from a poor OS group with high USC73 score (5-year OS = 83.3% and 13.3% respectively, HR = 40.1; p = 3 × 10-8). This finding was validated in the independent AU cohort (HR = 4.3; p = 0.0004). The poor prognosis group with high USC73 score consists of 37.9% and 32.8% of patients in the TCGA and AU cohort respectively. USC73 score and pathologic stage independently contribute to OS and together provide the best prognostic value. Early stage, low USC73 patients have the best prognosis (5-year OS = 85.1% in the combined dataset), while advanced stage, high USC73 patients have the worst prognosis (5-year OS = 6.4%, HR = 30.5, p = 1.2 × 10-12). Consistent with the observed poor survival, primary cell cultures from high USC73 patients had higher proliferation rate and cell cycle progression; and high USC73 patients had lower rates of complete response to standard therapy. CONCLUSIONS: The USC73 transcriptomic signature and stage independently predict OS of USC patients and the best prediction is achieved using USC73 and stage. USC73 may also serve as a therapeutic biomarker to guide patient care.
Subject(s)
Cystadenocarcinoma, Serous/genetics , Uterine Neoplasms/genetics , Aged , Aged, 80 and over , Cohort Studies , Cystadenocarcinoma, Serous/mortality , Cystadenocarcinoma, Serous/pathology , Cystadenocarcinoma, Serous/therapy , Disease Progression , Female , Humans , Middle Aged , Prognosis , Reproducibility of Results , Retrospective Studies , Sequence Analysis, RNA , Tissue Array Analysis , Transcriptome , Tumor Cells, Cultured , Uterine Neoplasms/mortality , Uterine Neoplasms/pathology , Uterine Neoplasms/therapyABSTRACT
Recent studies suggest that sleep-mediated consolidation processes help adults learn non-native speech sounds. However, overnight improvement was not seen when participants learned in the morning, perhaps resulting from native-language interference. The current study trained participants to perceive the Hindi dental/retroflex contrast in the morning and tested whether increased training can lead to overnight improvement. Results showed overnight effects regardless of training amount. In contrast to previous studies, participants in this study heard sounds in limited contexts (i.e., one talker and one vowel context), corroborating other findings, suggesting that overnight improvement is seen in non-native phonetic learning when variability is limited.
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BACKGROUND: Fertility counseling before cancer treatment has been advocated by clinical guidelines, though little is known about its long-term impact on the unique reproductive concerns of female adolescent and young adult (AYA) cancer survivors. The goal of this study was to measure the association between fertility counseling by fertility specialists before cancer treatment and subsequent reproductive concerns. METHOD: A cross-sectional analysis was performed among 747 AYA survivors aged 18-40 years who had been recruited from cancer registries and physician and advocacy group referrals between 2015 and 2017. Participants self-reported information on past fertility counseling at cancer diagnosis, cancer type and treatment, and current reproductive concerns, as measured using the multidimensional Reproductive Concerns After Cancer scale. Multivariable log-binomial regression models tested associations between fertility counseling and reproductive concerns. RESULTS: The mean age of the cohort was 33.0 years (standard deviation, 5.1 years), and the mean period since diagnosis was 7.7 years (standard deviation, 5.0 years). Seventy-three percent of participants were white, and 24% were Hispanic. Fertility counseling was reported by 19% of survivors; moderate to high overall reproductive concerns were reported by 44% of participants. In adjusted analysis, fertility counseling was significantly associated with moderate to high reproductive concerns (risk ratio, 1.22; 95% confidence interval, 1.02-1.45) and not modified by exposure to fertility-threatening treatments (Pinteraction = .23). CONCLUSION: A large proportion of AYA cancer survivors across cancer types and treatment exposures reported moderate to high reproductive concerns, suggesting that there is a need to address these cancer-specific reproductive health concerns after treatment. Higher concerns, even with counseling, suggests the need to improve the quality of fertility counseling throughout the cancer continuum.
Subject(s)
Cancer Survivors/psychology , Counseling/methods , Fertility , Neoplasms/therapy , Adolescent , Adult , Cohort Studies , Cross-Sectional Studies , Female , Fertility Preservation/methods , Humans , Neoplasms/psychology , Practice Guidelines as Topic , Young AdultABSTRACT
The speech signal is rife with variations in phonetic ambiguity. For instance, when talkers speak in a conversational register, they demonstrate less articulatory precision, leading to greater potential for confusability at the phonetic level compared with a clear speech register. Current psycholinguistic models assume that ambiguous speech sounds activate more than one phonological category and that competition at prelexical levels cascades to lexical levels of processing. Imaging studies have shown that the left inferior frontal gyrus (LIFG) is modulated by phonetic competition between simultaneously activated categories, with increases in activation for more ambiguous tokens. Yet, these studies have often used artificially manipulated speech and/or metalinguistic tasks, which arguably may recruit neural regions that are not critical for natural speech recognition. Indeed, a prominent model of speech processing, the dual-stream model, posits that the LIFG is not involved in prelexical processing in receptive language processing. In the current study, we exploited natural variation in phonetic competition in the speech signal to investigate the neural systems sensitive to phonetic competition as listeners engage in a receptive language task. Participants heard nonsense sentences spoken in either a clear or conversational register as neural activity was monitored using fMRI. Conversational sentences contained greater phonetic competition, as estimated by measures of vowel confusability, and these sentences also elicited greater activation in a region in the LIFG. Sentence-level phonetic competition metrics uniquely correlated with LIFG activity as well. This finding is consistent with the hypothesis that the LIFG responds to competition at multiple levels of language processing and that recruitment of this region does not require an explicit phonological judgment.