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Category-specific disorders are frequently explained by suggesting that living and non-living things are processed in separate subsystems (e.g. Caramazza & Shelton, 1998). If subsystems exist, there should be benefits for normal processing, beyond the influence of structural similarity. However, no previous study has separated the relative influences of similarity and semantic category. We created novel examples of living and non-living things so category and similarity could be manipulated independently. Pre-tests ensured that our images evoked appropriate semantic information and were matched for familiarity. Participants were trained to associate names with the images and then performed a name-verification task under two levels of time pressure. We found no significant advantage for living things alongside strong effects of similarity. Our results suggest that similarity rather than category is the key determinant of speed and accuracy in normal semantic processing. We discuss the implications of this finding for neuropsychological studies. [ABSTRACT FROM AUTHOR]

Immunotherapy combinations are being investigated to expand the benefit of immune checkpoint blockade across many cancer types. Radiation combinations, in particular using stereotactic body radiotherapy, are of keen interest because of underlying mechanistic rationale, safety, and availability as a standard of care in certain cancers. In addition to direct tumor cytotoxicity, radiation therapy has immunomodulatory effects such as induction of immunogenic cell death, enhancement of antigen presentation, and expansion of the T-cell receptor repertoire as well as recruitment and increased activity of tumor-specific effector CD8+ cells. Combinations of radiation with cytokines and/or chemokines and anti-programmed death 1 and anticytotoxic T-lymphocyte antigen 4 therapies have demonstrated safety and feasibility, as well as the potential to improve long-term outcomes and possibly induce out of irradiated field or abscopal responses. Novel immunoradiotherapy combinations represent a promising therapeutic approach to overcome radioresistance and further enhance systemic immunotherapy. Potential benefits include reversing CD8+ T-cell exhaustion, inhibiting myeloid-derived suppressor cells, and reversing M2 macrophage polarization as well as decreasing levels of colony-stimulating factor-1 and transforming growth factor-β. Here, we discuss current data and mechanistic rationale for combining novel immunotherapy agents with radiation therapy., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Complex diseases have multifactorial etiologies making actionable diagnostic biomarkers difficult to identify. Diagnostic research must expand beyond single or a handful of genetic or epigenetic targets for complex disease and explore a broader system of biological pathways. With the objective to develop a diagnostic tool designed to analyze a comprehensive network of epigenetic profiles in complex diseases, we used publicly available DNA methylation data from over 2,400 samples representing 20 cell types and various diseases. This tool, rather than detecting differentially methylated regions at specific genes, measures the intra-individual methylation variability within gene promoters to identify global shifts away from healthy regulatory states. To assess this new approach, we explored three distinct questions: 1) Are profiles of epigenetic variability tissue-specific? 2) Do diseased tissues exhibit altered epigenetic variability compared to normal tissue? 3) Can epigenetic variability be detected in complex disease? Unsupervised clustering established that global epigenetic variability in promoter regions is tissue-specific and promoter regions that are the most epigenetically stable in a specific tissue are associated with genes known to be essential for its function. Furthermore, analysis of epigenetic variability in these most stable regions distinguishes between diseased and normal tissue in multiple complex diseases. Finally, we demonstrate the clinical utility of this new tool in the assessment of a multifactorial condition, male infertility. We show that epigenetic variability in purified sperm is correlated with live birth outcomes in couples undergoing intrauterine insemination (IUI), a common fertility procedure. Men with the least epigenetically variable promoters were almost twice as likely to father a child than men with the greatest number of epigenetically variable promoters. Interestingly, no such difference was identified in men undergoing in vitro fertilization (IVF), another common fertility procedure, suggesting this as a treatment to overcome higher levels of epigenetic variability when trying to conceive., Competing Interests: RM, CP, KB, AO, RB, LL, JH, KA, and TJ are involved with Inherent Biosciences in one or a combination of the following capacities: employee, intern, advisor, equity-holder. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer XC declared a shared affiliation with the author LL to the handling editor at the time of review., (Copyright © 2023 Miller, Pollard, Brogaard, Olson, Barney, Lipshultz, Johnstone, Ibrahim, Hotaling, Schisterman, Mumford, Aston and Jenkins.)

Purpose: To report patient-reported outcomes (PROs) of a phase III trial evaluating total androgen suppression (TAS) combined with dose-escalated radiation therapy (RT) for patients with intermediate-risk prostate cancer., Methods: Patients with intermediate-risk prostate cancer were randomly assigned to dose-escalated RT alone (arm 1) or RT plus TAS (arm 2) consisting of luteinizing hormone-releasing hormone agonist/antagonist with oral antiandrogen for 6 months. The primary PRO was the validated Expanded Prostate Cancer Index Composite (EPIC-50). Secondary PROs included Patient-Reported Outcome Measurement Information System (PROMIS)-fatigue and EuroQOL five-dimensions scale questionnaire (EQ-5D). PRO change scores, calculated for each patient as the follow-up score minus baseline score (at the end of RT and at 6, 12, and 60 months), were compared between treatment arms using a two-sample t test. An effect size of 0.50 standard deviation was considered clinically meaningful., Results: For the primary PRO instrument (EPIC), the completion rates were ≥86% through the first year of follow-up and 70%-75% at 5 years. For the EPIC hormonal and sexual domains, there were clinically meaningful ( P < .0001) deficits in the RT + TAS arm. However, there were no clinically meaningful differences by 1 year between arms. There were also no clinically meaningful differences at any time points between arms for PROMIS-fatigue, EQ-5D, and EPIC bowel/urinary scores., Conclusion: Compared with dose-escalated RT alone, adding TAS demonstrated clinically meaningful declines only in EPIC hormonal and sexual domains. However, even these PRO differences were transient, and there were no clinically meaningful differences between arms by 1 year.

Individual neurons or muscle cells express many G-protein-coupled receptors (GPCRs) for neurotransmitters and neuropeptides, yet it remains unclear how cells integrate multiple GPCR signals that all must activate the same few G-proteins. We analyzed this issue in the Caenorhabditis elegans egg-laying system, where multiple GPCRs on muscle cells promote contraction and egg laying. We genetically manipulated individual GPCRs and G-proteins specifically in these muscle cells within intact animals and then measured egg laying and muscle calcium activity. Two serotonin GPCRs on the muscle cells, Gα q -coupled SER-1 and Gα s -coupled SER-7, together promote egg laying in response to serotonin. We found that signals produced by either SER-1/Gα q or SER-7/Gα s alone have little effect, but these two subthreshold signals combine to activate egg laying. We then transgenically expressed natural or designer GPCRs in the muscle cells and found that their subthreshold signals can also combine to induce muscle activity. However, artificially inducing strong signaling through just one of these GPCRs can be sufficient to induce egg laying. Knocking down Gα q and Gα s in the egg-laying muscle cells induced egg-laying defects that were stronger than those of a SER-1/SER-7 double knockout, indicating that additional endogenous GPCRs also activate the muscle cells. These results show that in the egg-laying muscles multiple GPCRs for serotonin and other signals each produce weak effects that individually do not result in strong behavioral outcomes. However, they combine to produce sufficient levels of Gα q and Gα s signaling to promote muscle activity and egg laying. SIGNIFICANCE STATEMENT How can neurons and other cells gather multiple independent pieces of information from the soup of chemical signals in their environment and compute an appropriate response? Most cells express >20 GPCRs that each receive one signal and transmit that information through three main types of G-proteins. We analyzed how this machinery generates responses by studying the egg-laying system of C. elegans , where serotonin and multiple other signals act through GPCRs on the egg-laying muscles to promote muscle activity and egg laying. We found that individual GPCRs within an intact animal each generate effects too weak to activate egg laying. However, combined signaling from multiple GPCR types reaches a threshold capable of activating the muscle cells., (Copyright © 2023 the authors.)

BACKGROUNDWe previously demonstrated the safety of stereotactic body radiotherapy followed by pembrolizumab (SBRT+P) in patients with advanced solid tumors. This phase I clinical trial was expanded to study the safety of partial tumor irradiation (partial-Rx). We assessed irradiated local failure (LF) and clinical outcomes with correlations to biomarkers including CD8+ T cell radiomics score (RS) and circulating cytokines.METHODSPatients received SBRT to 2-4 metastases and pembrolizumab for up to 7 days after SBRT. Tumors measuring up to 65 cc received the full radiation dose (complete-Rx), whereas tumors measuring more than 65 cc received partial-Rx. Landmark analysis was used to assess the relationship between tumor response and overall survival (OS). Multivariable analysis was performed for RS and circulating cytokines.RESULTSIn the combined (expansion plus original) cohort, 97 patients (219 metastases) were analyzed and received SBRT+P. Forty-six (47%) patients received at least 1 partial-Rx treatment. There were 7 (7.2%)dose-limiting toxicities (DLTs). 1-year LF was 7.6% overall, and 13.3% and 5.4% for partial-Rx and complete-Rx tumors, respectively (HR 2.32, 95% CI 0.90-5.97, P = 0.08). The overall, unirradiated, and irradiated objective response rates were 22%, 12%, and 34%, respectively. Irradiated tumor response to SBRT+P was associated with prolonged OS; 1-year OS was 71% (responders), 42% (mixed-responders), and 0% (nonresponders) (P < 0.01). High-RS was significantly associated with improved LF, progression-free survival (PFS), and OS. Elevated circulating IL-8 was independently associated with inferior PFS and OS.CONCLUSIONSBRT+P is safe in patients with large, advanced solid tumors. Additional studies are warranted to assess noninferiority of complete versus partial irradiation of tumors in the setting of immunotherapy.TRIAL REGISTRATIONClinicaltrials.gov NCT02608385FUNDINGMerck Investigator Studies Program; Hillman Fellows for Innovative Cancer Research Program; NIH grants UM1CA186690-06, P50CA254865-01A1, P30CA047904-32, and R01DE031729-01A1.

Ewing sarcoma is a fusion-oncoprotein-driven primary bone tumor most commonly diagnosed in adolescents. Given the continued poor outcomes for patients with metastatic and relapsed Ewing sarcoma, testing innovative therapeutic approaches is essential. Ewing sarcoma has been categorized as a 'BRCAness' tumor with emerging data characterizing a spectrum of DNA damage repair defects within individual Ewing tumors, including the presence of EWSR1::FLI1 itself, recurrent somatic mutations, and rare germline-based defects. It is critical to understand the cumulative impact of various DNA damage repair defects on an individual Ewing tumor's response to therapy. Further, in addition to DNA-damage-directed therapies, subsets of Ewing tumors may be more susceptible to DNA-damage/immunotherapy combinations given the significant cross-talk between DNA damage and inflammatory pathways in the tumor microenvironment. Here we review potential approaches utilizing DNA-damaging agents as modulators of the Ewing tumor immune microenvironment, with a focus on radiation and opportunities during disease metastasis and relapse., Competing Interests: AO receives research funding from Varian Medical Systems, Reflexion Medical and serves as a consultant for RenovoRx. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Daley, Olson and Bailey.)

Aims: The aims of the study were to compare characteristics, resources, benefits and outcomes of academic-clinical collaborations of nursing researcher leaders from academic, clinical and joint-employer sites., Background: Few research-based publications addressed academic-clinical research collaborations. New knowledge could increase nursing and multidisciplinary research productivity, including implementation science., Design: An anonymous survey using a 40-item questionnaire., Methods: Information letters with a link to the questionnaire were emailed to United States nursing research leaders. Data were grouped by institution type: academic, clinical or joint-employer. Analyses included Kruskal-Wallis tests for ordered responses, Pearson's chi-square test or Fisher's exact test for categorical responses and Cohen's Kappa agreement statistic for expected and actual time devoted to research. STROBE guidelines were followed., Results: Of 120 respondents from academic (n = 60; 50.0%), clinical (n = 53; 41.2%) and joint-employer (n = 7; 5.8%) sites, 78.3%, 92.3% and 100%, respectively, were from metropolitan areas. Mean (SD) priority for active collaborations was higher at joint-employer sites; p = .002. Clinical sites were more likely to have directors of evidence-based practice (p = .031) and informatics (p = .008) and librarians (p = .029). Sites with collaborations were more likely to have access to research subjects (p = .008) and post-award research account management (p = .045). By collaboration status, there were no differences in the number of ethics board-approved studies. Collaborating site benefits were perceived to be executive leadership support (p = .003), greater research engagement by clinical nurses (p = .048), more co-authored publications (p = .048) and more abstracts accepted at national meetings (p = .044). Despite more resources and perceived benefits, outcomes did not differ by collaboration status., Conclusions: Sites with and without academic-clinical research collaborations differed; however, outcomes were similar. Future efforts should focus on nurse scientist collaboration to address important clinical questions aimed at improving clinical outcomes., Relevance to Clinical Practice: Despite some successful outcomes, potential benefits of academic-clinical research collaborations have not been fully actualised., (© 2020 John Wiley & Sons Ltd.)

Purpose: The aim of this study was to examine current practice patterns in pediatric total body irradiation (TBI) techniques among COG member institutions., Methods and Materials: Between November 2019 and February 2020, a questionnaire containing 52 questions related to the technical aspects of TBI was sent to medical physicists at 152 COG institutions. The questions were designed to obtain technical information on commonly used TBI treatment techniques. Another set of 9 questions related to the clinical management of patients undergoing TBI was sent to 152 COG member radiation oncologists at the same institutions., Results: Twelve institutions were excluded because TBI was not performed in their institutions. A total of 88 physicists from 88 institutions (63% response rate) and 96 radiation oncologists from 96 institutions (69% response rate) responded. The anterior-posterior/posterior-anterior (AP/PA) technique was the most common technique reported (49 institutions [56%]); 44 institutions (50%) used the lateral technique, and 14 (16%) used volumetric modulated arc therapy or tomotherapy. Midplane dose rates of 6 to 15 cGy/min were most commonly used. The most common specification for lung dose was the midlung dose for both AP/PA techniques (71%) and lateral techniques (63%). Almost all physician responders agreed with the need to refine current TBI techniques, and 79% supported the investigation of new TBI techniques to further lower the lung dose., Conclusions: There was no consistency in the practice patterns, methods for dose measurement, and reporting of TBI doses among COG institutions. The lack of standardization precludes meaningful correlation between TBI doses and clinical outcomes including disease control and normal tissue toxicity. The COG radiation oncology discipline is currently undertaking several steps to standardize the practice and dose reporting of pediatric TBI using detailed questionnaires and phantom-based credentialing for all COG centers., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Individuals with dyslexia do not only show deficits with reading but are also less accurate in naming pictures. This has mainly been linked to prevalent phonological deficits. However, deficits in lexical retrieval of picture names could also be due to increased lexical-semantic competition. The present study tested whether adults with dyslexia (AwDs) are more affected by a competitive lexical-semantic context than control participants., Method: Twenty-seven AwD and 34 control participants completed the blocked-cyclic picture-naming paradigm and the Hayling sentence completion task., Results: In the blocked-cyclic naming task, AwDs showed a larger semantic interference effect than controls in terms of errors, especially producing competitor errors. In the Hayling sentence completion task, AwDs made more errors than controls when asked to complete sentences with semantically unrelated words, that is, in the competitive condition. They especially produced semantically related words or antonyms to target words., Conclusions: We found that AwDs experience difficulties with resolving lexical competition that go beyond their phonological deficits. Future studies will need to establish the mechanisms behind the increased lexical competition that AwDs exhibit. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Gαo is the alpha subunit of the major heterotrimeric G protein in neurons and mediates signaling by every known neurotransmitter, yet the signaling mechanisms activated by Gαo remain to be fully elucidated. Genetic analysis in Caenorhabditis elegans has shown that Gαo signaling inhibits neuronal activity and neurotransmitter release, but studies of the molecular mechanisms underlying these effects have been limited by lack of tools to complement genetic studies with other experimental approaches. Here, we demonstrate that inserting the green fluorescent protein (GFP) into an internal loop of the Gαo protein results in a tagged protein that is functional in vivo and that facilitates cell biological and biochemical studies of Gαo. Transgenic expression of Gαo-GFP rescues the defects caused by loss of endogenous Gαo in assays of egg laying and locomotion behaviors. Defects in body morphology caused by loss of Gαo are also rescued by Gαo-GFP. The Gαo-GFP protein is localized to the plasma membrane of neurons, mimicking localization of endogenous Gαo. Using GFP as an epitope tag, Gαo-GFP can be immunoprecipitated from C. elegans lysates to purify Gαo protein complexes. The Gαo-GFP transgene reported in this study enables studies involving in vivo localization and biochemical purification of Gαo to compliment the already well-developed genetic analysis of Gαo signaling., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)

Aims: National studies have demonstrated disparities in the treatment and survival of pancreatic cancer patients based on socioeconomic status (SES). This study aimed to identify specific differences in perioperative management and outcomes based on patient SES and to study the role of a multidisciplinary clinic (MDC) in mitigating any variations., Methods: The study analyzed patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma in a large hospital system. The patients were categorized into groups of high and low SES and whether they were managed by the authors' pancreatic cancer MDC or not. The study compared differences in disease characteristics, receipt of multimodality therapy, perioperative outcomes, and recurrence-free and overall survival., Results: Of the 162 low-SES patients and 119 high-SES patients, 54% were managed in the MDC. Outside the MDC, low-SES patients were less likely to receive neoadjuvant chemotherapy and had less minimally invasive surgery, a longer OR time, less enhanced recovery participation, and more major complications (p < 0.05). No SES disparities were observed among the MDC patients. Despite similar tumor characteristics, the low-SES patients had inferior median overall survival (21 vs 32 months; p = 0.005), but the MDC appeared to eliminate this disparity. Low SES correlated with inferior survival for the non-MDC patients (17 vs 32 months; p < 0.001), but not for the MDC patients (24 vs 25 months; p = 0.33). These findings persisted in the multivariable analysis., Conclusion: A pancreatic cancer MDC standardizes treatment decisions, eliminates disparities in surgical outcomes, and improves survival for low-SES patients.

Introduction: Infants of mothers with substance use disorder (SUD) are exposed to complex social environments and increased childhood health risks that can lead to adverse consequences throughout the lifespan. GunderKids, a voluntary, specialized, comprehensive pediatric care management program, was developed to mitigate many of these adverse consequences. Our organization is evaluating several clinical outcomes related to health and development in children born to women with SUD. The current study addressed the timeliness of vaccination coverage among these infants. Methods: This descriptive comparative preliminary study evaluated data of infants and their mothers with SUD who were previously identified during prenatal care visits either by self-report or by positive urine screens. Sociodemographic and vaccination data were extracted from a longitudinal master dataset of variables developed and maintained through retrospective review of electronic health records (EHRs) of these mothers and their infants. Timeliness of vaccination coverage of SUD-exposed infants participating in GunderKids was compared with that of SUD-exposed infants receiving standard pediatric care and was determined using a cumulative vaccinations method. Results: Overall, infants in the GunderKids group (n=50) had more timely vaccination coverage than those receiving standard pediatric care (n=20). Examples of timelier coverage included Haemophilus influenzae type b (Hib) at 4 months ( P = .01; OR 4.3, 95% CI 1.4-13.4), for pneumococcal ( P = .004; OR 6.6, 95% CI 1.8-23.8) and Hib ( P = .004; OR 5.8, 95% CI 1.6-21.9) vaccinations at 15 months. More than 77% of GunderKids received all 6-month vaccinations in a timely manner compared with less than 45% of the standard care group; odds ratios suggest that GunderKids had 4.0-5.6 higher odds of receiving 6-month vaccinations. Conclusion: Vaccination coverage of infants participating in GunderKids was timelier than that of infants receiving standard pediatric care. Results suggest that specialized programs like GunderKids may assist in mitigating adverse health consequences and timeliness of vaccination coverage might be used as a proxy for measuring program effectiveness. Further investigation is recommended to determine clinical, individual, and organizational factors that influence parental behaviors and pediatric outcomes within SUD-exposed families., (Copyright © 2021 Marshfield Clinic Health System.)

Purpose: Treatment with radiation therapy (RT) can cause anxiety and distress for pediatric patients and their families. Radiation oncology teams have developed strategies to reduce the negative psychological impact. This survey study aimed to characterize these methods., Methods and Materials: A 37-item questionnaire was sent to all radiation oncology members of the Children's Oncology Group to explore strategies to improve the pediatric patient experience. The Wilcoxon rank-sum test was used to assess factors associated with use of anesthesia for older children., Results: Surveys were completed by 106 individuals from 84/210 institutions (40%). Respondents included 89 radiation oncologists and 17 supportive staff. Sixty-one percent of centers treated ≤50 children per year. Respondents described heterogenous interventions. The median age at which most children no longer required anesthesia was 6 years (range: ≤3 years to ≥8 years). Routine anesthesia use at an older age was associated with physicians' lack of awareness of these strategies (P = .04) and <10 years of pediatric radiation oncology experience (P = .04). Fifty-two percent of respondents reported anesthesia use added >45 minutes in the radiation oncology department daily. Twenty-six percent of respondents planned to implement new strategies, with 65% focusing on video-based distraction therapy and/or augmented reality/virtual reality., Conclusions: Many strategies are used to improve children's experience during RT. Lack of awareness of these interventions is a barrier to their implementation and is associated with increased anesthesia use. This study aims to disseminate these methods with the goal of raising awareness, facilitating implementation, and, ultimately, improving the experience of pediatric cancer patients and their caregivers., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: There is no consensus on treatment volumes for adjuvant stereotactic body radiation therapy (SBRT) for pancreatic cancer. Herein, we report patterns of failure after pancreatic SBRT for close/positive margins, which may inform target volume design., Methods and Materials: An institutional review board-approved retrospective review of patients with pancreatic adenocarcinoma treated with adjuvant SBRT for close/positive margins from 2009 to 2018 was conducted. Patterns of failure were defined as local (LF) within the tumor bed, regional (RF) within lymph nodes or anastomoses, or distant (DF). The cumulative incidence of locoregional failure was calculated using the cumulative incidence function accounting for the competing risk of death. LFs were mapped to the planning target volume (PTV) and classified as in-field (completely within the PTV), marginal (partially within the PTV), or out-of-field (completely outside the PTV). The location of LFs was compared with the Radiation Therapy Oncology Group 0848 contouring atlas to determine whether standard postoperative radiation therapy volumes would have included the LF., Results: Seventy-six patients were treated with adjuvant SBRT for close (51.3%) or positive (48.7%) margins. Most (81.6%) received 36 Gy in 3 fractions, with a median PTV volume of 17.8 cc (interquartile range, 12.1-25.6). With a median follow-up of 17.0 months (interquartile range, 7.3-28.4), crude rates of first isolated LF, isolated RF, and DF +/- LF or RF were 9.2%, 6.6%, and 56.6%, respectively. Two-year cumulative incidences of LF, RF, locoregional failure, and DF were 34.9%, 30.8%, 49.2%, and 60.4%, respectively. Of 28 reviewable LFs, 21.4% were in-field while the remainder were completely outside (60.7%) or partially outside (17.9%) the PTV. Most LFs (92.9%) would have been encompassed by the Radiation Therapy Oncology Group consensus target volumes., Conclusions: After adjuvant pancreatic SBRT for close/positive margins, the majority of LFs were outside the PTV but within contemporary target volumes for conventional radiation therapy., (© 2020 Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.)

Purpose: To describe cancer incidence and treatment utilization patterns at the regional cancer referral center for the Lake Zone of northwestern Tanzania from 2008 to 2016., Methods: This descriptive, retrospective study reviewed all cancer cases recorded in the Bugando Cancer Registry (BCR), a clinical and pathology based registry at the only cancer referral hospital in the region. Primary tumor site, method of diagnosis, HIV status, and cancer treatment were reported. Using census data, the 2012 GLOBOCAN estimates for Tanzania were scaled to the Lake Zone and adjusted for 2016 population growth. These estimates were then compared to BCR cases using one-sample tests of proportion., Results: A total of 2772 cases were reported from 2008-2016. Among these, the majority of cases (82.5 %, n = 2286) were diagnosed among adults. Most cases (85 %, n = 1923) were diagnosed by histology or cytology. Among adults, the most common cancers diagnosed were cervix (22.7 %, n=520), breast (12.6 %, n=288), and prostate (8.5 %, n=195). Among children, the most common cancers were non-Burkitt non-Hodgkin lymphoma (17.3 %, n=84), Burkitt lymphoma (16.5 %, n=80), and Wilms tumor (14.6 %, n=71). The 1116 BCR cases represent 12.2 % of the 9165 expected number of cancer cases for the Lake Zone (p < 0.001). 1494 cases (53.9 %) received some form of treatment - surgery, chemotherapy, radiation, or hormone therapy - while 1278 cases (46.1 %) had no treatment recorded., Conclusions: This comprehensive report of the BCR reveals cancer epidemiology and treatment utilization patterns typical of hospitals in low-resource settings. Despite being the only cancer center in the Lake Zone, BMC evaluates a small percentage of the expected number of cancer patients for the region. The BCR remains an important resource to guide clinical care and academic activities for the Lake Zone., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The sophistication of gene prediction algorithms and the abundance of RNA-based evidence for the maize genome may suggest that manual curation of gene models is no longer necessary. However, quality metrics generated by the MAKER-P gene annotation pipeline identified 17,225 of 130,330 (13%) protein-coding transcripts in the B73 Reference Genome V4 gene set with models of low concordance to available biological evidence. Working with eight graduate students, we used the Apollo annotation editor to curate 86 transcript models flagged by quality metrics and a complimentary method using the Gramene gene tree visualizer. All of the triaged models had significant errors-including missing or extra exons, non-canonical splice sites, and incorrect UTRs. A correct transcript model existed for about 60% of genes (or transcripts) flagged by quality metrics; we attribute this to the convention of elevating the transcript with the longest coding sequence (CDS) to the canonical, or first, position. The remaining 40% of flagged genes resulted in novel annotations and represent a manual curation space of about 10% of the maize genome (~4,000 protein-coding genes). MAKER-P metrics have a specificity of 100%, and a sensitivity of 85%; the gene tree visualizer has a specificity of 100%. Together with the Apollo graphical editor, our double triage provides an infrastructure to support the community curation of eukaryotic genomes by scientists, students, and potentially even citizen scientists., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose: Antibodies against programmed cell death protein 1 (PD-1) are standard treatments for advanced melanoma. Palliative radiation therapy (RT) is commonly administered for this disease. Safety and optimal timing for this combination for melanoma has not been established., Materials and Methods: In this retrospective cohort study, records for melanoma patients who received anti-PD-1 therapy at Duke University or Emory University (1/1/2013-12/30/2015) were reviewed. Patients were categorized by receipt of RT and RT timing relative to anti-PD-1., Results: 151 patients received anti-PD-1 therapy. Median follow-up was 12.9 months. Patients receiving RT (n = 85) had worse baseline prognostic factors than patients without RT (n = 66). One-year overall survival (OS) was lower for RT patients than patients without RT (66%, 95% CI: 55-77% vs 83%, 95% CI: 73-92%). One-year OS was 61% for patients receiving RT before anti-PD-1 (95% CI: 46-76%), 78% for RT during anti-PD-1 (95% CI: 60-95%), and 58% for RT after anti-PD-1 (95% CI: 26-89%). On Cox regression, OS for patients without RT did not differ significantly from patients receiving RT during anti-PD-1 (HR 1.07, 95% CI: 0.41-2.84) or RT before anti-PD-1 (HR 0.56, 95% CI: 0.21-1.45). RT and anti-PD-1 therapy administered within 6 weeks of each other was well tolerated., Conclusion: RT can be safely administered with anti-PD-1 therapy. Despite worse baseline prognostic characteristics for patients receiving RT, OS was similar for patients receiving concurrent RT with anti-PD-1 therapy compared to patients receiving anti-PD-1 therapy alone., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Doctoral prepared nurse practitioners (NPs) are uniquely positioned for responsible leadership as essential members of the health care system and have a professional responsibility to contribute to research and clinical inquiry initiatives that advance health care delivery and improve outcomes. Academic preparation of the Doctor of Philosophy (PhD) and Doctor of Nursing Practice (DNP), although different in focus, offers opportunities for effective collaborations that transcend and integrate the scientific and practice roles of generating data and translating evidence. As health care organizations evolve in managing complexities of providing high-quality care, roles for the PhD as research scientist and DNP as research translation specialist will also evolve to keep pace. Despite this professional calling and global opportunity for research and evidence-based practice (EBP), future NPs and nurses will be challenged with an imminent lack of experts who have the skills needed for data and research generation and evidence translation. This commentary introduces and discusses emerging roles and organizational models for doctoral prepared NPs in research, EBP, quality assurance, and quality improvement projects, offers suggestions for NPs interested in research and clinical inquiry, and seeks to ignite excitement for scientific discovery in NP-driven initiatives. Nurse practitioners are encouraged to take advantage of the many opportunities to shape and expand their careers by engaging in knowledge generation for improving health care outcomes.

Academic-clinical research partnerships can benefit academic and clinical partners when goals are clearly articulated and mutually determined and include increased research dissemination and lower research costs. This article explores the history of academic-clinical research partnerships and discusses the drivers of collaborative academic-clinical research relationships, resources from academia and clinical sites, and sustainability of collaborative partnerships. Through collaboration, academic-clinical partners can improve clinical outcomes and reduce healthcare costs.

Neurons typically release both a small-molecule neurotransmitter and one or more neuropeptides, but how these two types of signal from the same neuron might act together remains largely obscure. For example, serotonergic neurons in mammalian brain express the neuropeptide Substance P, but it is unclear how this co-released neuropeptide might modulate serotonin signaling. We studied this issue in C. elegans, in which all serotonergic neurons express the neuropeptide NLP-3. The serotonergic Hermaphrodite Specific Neurons (HSNs) are command motor neurons within the egg-laying circuit which have been shown to release serotonin to initiate egg-laying behavior. We found that egg-laying defects in animals lacking serotonin were far milder than in animals lacking HSNs, suggesting that HSNs must release other signal(s) in addition to serotonin to stimulate egg laying. While null mutants for nlp-3 had only mild egg-laying defects, animals lacking both serotonin and NLP-3 had severe defects, similar to those of animals lacking HSNs. Optogenetic activation of HSNs induced egg laying in wild-type animals, and in mutant animals lacking either serotonin or NLP-3, but failed to induce egg laying in animals lacking both. We recorded calcium activity in the egg-laying muscles of animals lacking either serotonin, NLP-3, or both. The single mutants, and to a greater extent the double mutant, showed muscle activity that was uncoordinated and unable to expel eggs. Specifically, the vm2 muscles cells, which are direct postsynaptic targets of the HSN, failed to contract simultaneously with other egg-laying muscle cells. Our results show that the HSN neurons use serotonin and the neuropeptide NLP-3 as partially redundant co-transmitters that together stimulate and coordinate activity of the target cells onto which they are released., Competing Interests: The authors have declared that no competing interests exist.

Background: To synthesize published literature on the association between human immunodeficiency virus (HIV) infection and radiation therapy (RT)-related toxicities. Methods: Two electronic databases, MEDLINE and Embase, were searched to identify studies published before November 2016 comparing RT-related toxicities between HIV-infected and HIV-uninfected patients receiving RT or chemoradiation therapy (CRT) for cancer. A qualitative synthesis of included articles and organ-specific toxicities was then performed. Results: Of the 21 studies included in this review, 15 reported on anal cancer treatment, three on cervical cancer, two on Kaposi sarcoma, and one on prostate cancer. Reports in the pre-antiretroviral therapy (ART) or early ART era tended to identify increased morbidity and mortality with HIV infection. However, modern series incorporating more concurrent chemotherapy, conformal RT techniques, and ART administration result in fewer studies reporting toxicity differences in patients treated for anal and cervical cancers. When statistically significant, HIV-infected patients had higher rates of gastrointestinal toxicity with anal cancer CRT (up to 50%) and higher rates of hematologic toxicity with cervical cancer CRT (up to 31%). Of the 17 studies reporting treatment outcomes, nine suggest HIV-infected patients may have reduced local control and/or survival rates. Conclusions: Overall, RT is likely similarly tolerated between HIV-infected and HIV-uninfected patients, especially with modern RT techniques. HIV-infected patients should continue to receive established standard of care RT and CRT dosing.

The isolation of [K(2.2.2-cryptand)][Ln(C 5 H 4 SiMe 3 ) 3 ], formally containing Ln II , for all lanthanides (excluding Pm ) was surprising given that +2 oxidation states are typically regarded as inaccessible for most 4f-elements. Herein, X-ray absorption near-edge spectroscopy (XANES), ground-state density functional theory (DFT), and transition dipole moment calculations are used to investigate the possibility that Ln(C 5 H 4 SiMe 3 ) 3 1- (Ln = Pr, Nd, Sm, Gd, Tb, Dy, Y, Ho, Er, Tm, Yb and Lu) compounds represented molecular Ln II complexes. Results from the ground-state DFT calculations were supported by additional calculations that utilized complete-active-space multi-configuration approach with second-order perturbation theoretical correction (CASPT2). Through comparisons with standards, Ln(C 5 H 4 SiMe 3 ) 3 1- (Ln = Sm, Tm, Yb, Lu, Y) are determined to contain 4f 6 5d 0 (Sm II ), 4f 13 5d 0 (Tm II ), 4f 14 5d 0 (Yb II ), 4f 14 5d 1 (Lu II ), and 4d 1 (Y II ) electronic configurations. Additionally, our results suggest that Ln(C 5 H 4 SiMe 3 ) 3 1- (Ln = Pr, Nd, Gd, Tb, Dy, Ho, and Er) also contain Ln II ions, but with 4f n 5d 1 configurations (not 4f n +1 5d 0 ). In these 4f n 5d 1 complexes, the C 3h -symmetric ligand environment provides a highly shielded 5d-orbital of a ' symmetry that made the 4f n 5d 1 electronic configurations lower in energy than the more typical 4f n +1 5d 0 configuration.

Rising cancer incidence and mortality in India emphasize the need to address the increasing burden of this disease and the stark inequities in access to radiotherapy and other essential medical treatments. State-of-the-art technology is available within the private sector and a few hospitals in the public sector, but 75% of patients in the public sector in India do not have access to timely radiotherapy. This inequity in access to radiotherapy in the public sector is amplified in rural areas, where most of India׳s population lives. A long-term government commitment to machine purchase and human resource development in the public sector is needed to improve access. A number of innovative initiatives to improve cancer treatment and access have emerged that could support such an investment. These include local production of equipment, twinning programs between institutions in high- and low-income countries to exchange knowledge and expertise, and nongovernmental and state-sponsored schemes to sponsor and support patients in their cancer journey. Strengthening of cancer registries and regulatory bodies with authority to enforce minimum standards is also required to improve care. The more uniform and frequent availability of high-quality radiotherapy can improve cancer outcomes and may be regarded as a marker of a comprehensive and equitable system of health care delivery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This study aimed to report hippocampal dose from single-fraction stereotactic radiosurgery (SRS) for 4 to 10 brain metastases and determine feasibility of hippocampal-sparing SRS. Patients with 4 to 10 brain metastases receiving single-isocenter, multi-target single-fraction SRS were identified. Hippocampi were contoured using the Radiation Therapy Oncology Group (RTOG) 0933 atlas. RTOG 0933 dose constraints were converted to a biologically effective dose using an alpha/beta of 2 (D 100 421 cGy, D max 665 cGy). Number of metastases, total target volume, prescribed dose, and distance of nearest metastasis (dmin) were analyzed as risk factors for exceeding hippocampal constraints. If hippocampi exceeded constraints, the SRS plan was re-optimized. Key dosimetric parameters were compared between original and re-optimized plans. To determine if a single target can exceed constraints, all targets but the closest metastasis were removed from the plan, and dosimetry was compared. Forty plans were identified. Fifteen hippocampi (19%) exceeded constraints in 12 SRS plans. Hippocampal sparing was achieved in 10 of 12 replanned cases (83%). Risk factors associated with exceeding hippocampal constraints were decreasing dmin (24.0 vs 8.0 mm, p = 0.002; odds ratio [OR] 1.14, 95% confidence interval [CI] 1.04 to 1.26) and total target volume (5.46 cm 3 vs 1.98 cm 3 , p = 0.03; OR 1.14, 95% CI 1.00 to 1.32). There was no difference in exceeding constraints for 4 to 5 vs 6 to 10 metastases (27% vs 21%, p = 0.409) or prescribed dose (18 Gy, p = 0.58). For re-optimized plans, there were no significant differences in planning target volume (PTV) coverage (99.6% vs 99.0%, p = 0.17) or conformality index (1.47 vs 1.4, p = 0.78). Six (50%) plans exceeded constraints with a single target. A substantial minority of hippocampi receive high radiation dose from SRS for 4 to 10 brain metastases. Decreasing distance of the closest metastasis and total target volume are associated with exceeding hippocampal constraints. Re-optimizing these plans yielded hippocampal-sparing SRS plans with acceptable dosimetry. Prospective evaluation of the impact of hippocampal dose from SRS on neurocognition merits consideration., (Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose: Patients with melanoma treated with ipilimumab and radiosurgery (stereotactic radiosurgery [SRS]) were reviewed for efficacy/safety., Methods: Patients who received ipilimumab and SRS for brain metastases were analyzed for control of SRS-treated metastasis and overall survival., Results: We identified 27 patients, 26 were assessable for outcomes. Median time-to-treated metastasis progression was 6.3 months (95% CI: 3.1-12.2). Overall survival was 23.4 months (95% CI: 5.7-not estimable) for SRS prior to/during ipilimumab (n = 14), and 10.4 months (95% CI: 1.9-not estimable) for SRS after ipilimumab (n = 12). Overall, no unexpected toxicities were seen: 11% of patients experienced grade 3 CNS toxicity and 7% developed radionecrosis., Conclusion: SRS for melanoma brain metastases with ipilimumab was well-tolerated. There may be improved survival for patients receiving SRS prior to/during ipilimumab., Competing Interests: Financial & competing interests disclosure AKS Salama receives research funding and is a consultant for Bristol-Myers Squibb. She also receives research funding from Genentech, Merck, Reata and Celldex. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Nanoscale stress-sensing can be used across fields ranging from detection of incipient cracks in structural mechanics to monitoring forces in biological tissues. We demonstrate how tetrapod quantum dots (tQDs) embedded in block copolymers act as sensors of tensile/compressive stress. Remarkably, tQDs can detect their own composite dispersion and mechanical properties with a switch in optomechanical response when tQDs are in direct contact. Using experimental characterizations, atomistic simulations and finite-element analyses, we show that under tensile stress, densely packed tQDs exhibit a photoluminescence peak shifted to higher energies ("blue-shift") due to volumetric compressive stress in their core; loosely packed tQDs exhibit a peak shifted to lower energies ("red-shift") from tensile stress in the core. The stress shifts result from the tQD's unique branched morphology in which the CdS arms act as antennas that amplify the stress in the CdSe core. Our nanocomposites exhibit excellent cyclability and scalability with no degraded properties of the host polymer. Colloidal tQDs allow sensing in many materials to potentially enable autoresponsive, smart structural nanocomposites that self-predict impending fracture.

The unicellular green algae Chlamydomonas reinhardtii has long been studied for its unique fermentation pathways and has been evaluated as a candidate organism for biofuel production. Fermentation in C. reinhardtii is facilitated by a network of three predominant pathways producing four major byproducts: formate, ethanol, acetate and hydrogen. Previous microarray studies identified many genes as being highly up-regulated during anaerobiosis. For example, hybrid cluster protein 4 (HCP4) was found to be one of the most highly up-regulated genes under anoxic conditions. Hybrid cluster proteins have long been studied for their unique spectroscopic properties, yet their biological functions remain largely unclear. To probe its role during anaerobiosis, HCP4 was silenced using artificial microRNAs (ami-hcp4) followed by extensive phenotypic analyses of cells grown under anoxic conditions. Both the expression of key fermentative enzymes and their respective metabolites were significantly altered in ami-hcp4, with nitrogen uptake from the media also being significantly different than wild-type cells. The results strongly suggest a role for HCP4 in regulating key fermentative and nitrogen utilization pathways.

New members of the dithiophosphinic acid family of potential actinide extractants were prepared: heterocyclic 2,2'-biphenylenedithiophosphinic acids of stoichiometry HS2P(R2C12H6) (R = H or (t)Bu). The time- and atom-efficient syntheses afforded multigram quantities of pure HS2P(R2C12H6) in reasonable yields (∼60%). These compounds differed from other diaryldithiophosphinic acid extractants in that the two aryl groups were connected to one another at the ortho positions to form a 5-membered dibenzophosphole ring. These 2,2'-biphenylenedithiophosphinic acids were readily deprotonated to form S2P(R2C12H6)(1-) anions, which were crystallized as salts with tetraphenylpnictonium cations (ZPh4(1+); Z = P or As). Coordination chemistry between [S2P((t)Bu2C12H6)](1-) and [S2P(C6H5)2](1-) with U, Np, and Pu was comparatively investigated. The results showed that dithiophosphinate complexes of U(IV) and Np(IV) were redox stable relative to those of U(III), whereas reactions involving Pu(IV) gave intractable material. For instance, reactions involving U(IV) and Np(IV) generated An[S2P((t)Bu2C12H6)]4 and An[S2P(C6H5)2]4 whereas reactions between Pu(IV) and [S2P(C6H5)2](1-) generated a mixture of products from which we postulated a transient Pu(III) species based on UV-Vis spectroscopy. However, the trivalent Pu[S2P(C6H5)2]3(NC5H5)2 compound is stable and could be isolated from reactions between [S2P(C6H5)2](1-) and the trivalent PuI3(NC5H5)4 starting material. Attempts to synthesize analogous trivalent compounds with U(III) provided the tetravalent U[S2P(C6H5)2]4 oxidation product.

With the availability of nanoparticles with controlled size and shape, there has been renewed interest in the mechanical properties of polymer/nanoparticle blends. Despite the large number of theoretical studies, the effect of branching for nanofillers tens of nanometers in size on the elastic stiffness of these composite materials has received limited attention. Here, we examine the Young's modulus of nanocomposites based on a common block copolymer (BCP) blended with linear nanorods and nanoscale tetrapod Quantum Dots (tQDs), in electrospun fibers and thin films. We use a phenomenological lattice spring model (LSM) as a guide in understanding the changes in the Young's modulus of such composites as a function of filler shape. Reasonable agreement is achieved between the LSM and the experimental results for both nanoparticle shapes--with only a few key physical assumptions in both films and fibers--providing insight into the design of new nanocomposites and assisting in the development of a qualitative mechanistic understanding of their properties. The tQDs impart the greatest improvements, enhancing the Young's modulus by a factor of 2.5 at 20 wt.%. This is 1.5 times higher than identical composites containing nanorods. An unexpected finding from the simulations is that both the orientation of the nanoscale filler and the orientation of X-type covalent bonds at the nanoparticle-ligand interface are important for optimizing the mechanical properties of the nanocomposites. The tQD provides an orientational optimization of the interfacial and filler bonds arising from its three-dimensional branched shape unseen before in nanocomposites with inorganic nanofillers.

Covalency in Ln-Cl bonds of Oh-LnCl6(x-) (x = 3 for Ln = Ce(III), Nd(III), Sm(III), Eu(III), Gd(III); x = 2 for Ln = Ce(IV)) anions has been investigated, primarily using Cl K-edge X-ray absorption spectroscopy (XAS) and time-dependent density functional theory (TDDFT); however, Ce L3,2-edge and M5,4-edge XAS were also used to characterize CeCl6(x-) (x = 2, 3). The M5,4-edge XAS spectra were modeled using configuration interaction calculations. The results were evaluated as a function of (1) the lanthanide (Ln) metal identity, which was varied across the series from Ce to Gd, and (2) the Ln oxidation state (when practical, i.e., formally Ce(III) and Ce(IV)). Pronounced mixing between the Cl 3p- and Ln 5d-orbitals (t2g* and eg*) was observed. Experimental results indicated that Ln 5d-orbital mixing decreased when moving across the lanthanide series. In contrast, oxidizing Ce(III) to Ce(IV) had little effect on Cl 3p and Ce 5d-orbital mixing. For LnCl6(3-) (formally Ln(III)), the 4f-orbitals participated only marginally in covalent bonding, which was consistent with historical descriptions. Surprisingly, there was a marked increase in Cl 3p- and Ce(IV) 4f-orbital mixing (t1u* + t2u*) in CeCl6(2-). This unexpected 4f- and 5d-orbital participation in covalent bonding is presented in the context of recent studies on both tetravalent transition metal and actinide hexahalides, MCl6(2-) (M = Ti, Zr, Hf, U).

Herein, we have evaluated relative changes in M-S electronic structure and orbital mixing in Group 6 MS4(2-) dianions using solid- and solution-phase S K-edge X-ray absorption spectroscopy (XAS; M = Mo, W), as well as density functional theory (DFT; M = Cr, Mo, W) and time-dependent density functional theory (TDDFT) calculations. To facilitate comparison with solution measurements (conducted in acetonitrile), theoretical models included gas-phase calculations as well as those that incorporated an acetonitrile dielectric, the latter of which provided better agreement with experiment. Two pre-edge features arising from S 1s → e* and t electron excitations were observed in the S K-edge XAS spectra and were reasonably assigned as (1)A1 → (1)T2 transitions. For MoS4(2-), both solution-phase pre-edge peak intensities were consistent with results from the solid-state spectra. For WS4(2-), solution- and solid-state pre-edge peak intensities for transitions involving e* were equivalent, while transitions involving the t orbitals were less intense in solution. Experimental and computational results have been presented in comparison to recent analyses of MO4(2-) dianions, which allowed M-S and M-O orbital mixing to be evaluated as the principle quantum number (n) for the metal valence d orbitals increased (3d, 4d, 5d). Overall, the M-E (E = O, S) analyses revealed distinct trends in orbital mixing. For example, as the Group 6 triad was descended, e* (π*) orbital mixing remained constant in the M-S bonds, but increased appreciably for M-O interactions. For the t orbitals (σ* + π*), mixing decreased slightly for M-S bonding and increased only slightly for the M-O interactions. These results suggested that the metal and ligand valence orbital energies and radial extensions delicately influenced the orbital compositions for isoelectronic ME4(2-) (E = O, S) dianions.

This study investigated deaf adolescents' implicit and explicit awareness of subject-verb number agreement. In Experiment 1, a self-paced reading task, the reading times of deaf and hearing children (matched for reading and chronological age, mean=8;3 and 13;10 years) increased when sentences contained disagreeing subject-verb number markers. However, deaf adolescents' slowing occurred later in the sentence than it did in both groups of hearing children. The same deaf adolescents were unable to detect and correct subject-verb agreement errors in Experiment 2, whereas both groups of hearing children performed well on this task. Thus, deaf adolescents demonstrated implicit awareness of agreement in the absence of explicit knowledge. Moreover, this nascent awareness was below that expected on the basis of their (substantially delayed) reading ability. Therefore, grammatical difficulties could be a significant impediment to deaf children's literacy. Future research should examine whether this is a result of late or incomplete learning of English, bilingualism, or another factor.

The photochemical behavior of Deepwater Horizon oil collected from the surface of the Gulf of Mexico was studied. Thin oil films on water were subjected to simulated sunlight, and the resulting chemical and optical changes were observed. Polycyclic aromatic hydrocarbons (PAHs) showed substantial photodegradation, with larger PAHs being more rapidly decomposed. About 60% of the fluorescence at the excitation and emission maxima was observed with 12h of simulated solar irradiation equivalent to approximately 3d of sunlight. Synchronous scan fluorescence measurements showed 80-90% loss of larger PAHs with 12h of simulated solar irradiation. Absorbance of the oil decreased by only 20% over the same time period. Alkanes showed no significant photochemical losses. After irradiation, the toxicity of water in contact with the oil significantly increased, presumably due to the release of water soluble photoproducts that were toxic. Photocatalyst addition resulted in enhanced degradation rate for PAHs, and toxicity of the aqueous layer was altered in the presence of photocatalysts added to the oil film. Photochemistry is an important pathway for degradation of large PAHs, which are typically resistant to biodegradation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

A nanoscale, visible-light, self-sensing stress probe would be highly desirable in a variety of biological, imaging, and materials engineering applications, especially a device that does not alter the mechanical properties of the material it seeks to probe. Here we present the CdSe-CdS tetrapod quantum dot, incorporated into polymer matrices via electrospinning, as an in situ luminescent stress probe for the mechanical properties of polymer fibers. The mechanooptical sensing performance is enhanced with increasing nanocrystal concentration while causing minimal change in the mechanical properties even up to 20 wt % incorporation. The tetrapod nanoprobe is elastic and recoverable and undergoes no permanent change in sensing ability even upon many cycles of loading to failure. Direct comparisons to side-by-side traditional mechanical tests further validate the tetrapod as a luminescent stress probe. The tetrapod fluorescence stress-strain curve shape matches well with uniaxial stress-strain curves measured mechanically at all filler concentrations reported.