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PURPOSE To determine the specific types, durations, and intensities of recreational physical activity associated with the greatest improvements in disease-free survival (DFS) of patients with colon cancer. METHODS We conducted a prospective cohort study nested within a randomized multicenter trial of stage III colon cancer that compared 3 versus 6 months of fluorouracil, leucovorin, and oxaliplatin with or without celecoxib. We measured recreational physical activity in the first 3 months of chemotherapy and again 6 months after completion of chemotherapy. The primary end point was DFS. RESULTS During a median follow-up of 5.9 years, 457 of 1,696 patients experienced disease recurrence or death. For total recreational physical activity volume, the 3-year DFS was 76.5% with < 3.0 metabolic equivalent task hours per week (MET-h/wk) and 87.1% with ≥ 18.0 MET-h/wk (risk difference [RD], 10.6%; 95% CI, 4.7 to 19.4; P < .001). For light-intensity to moderate-intensity activities, the 3-year DFS was 65.7% with 0.0 h/wk and 87.1% with ≥ 1.5 h/wk (RD, 21.4%; 95% CI, 9.2 to 37.1; P < .001). For vigorous-intensity activity, the 3-year DFS was 76.0% with 0.0 h/wk and 86.0% with ≥ 1.0 h/wk (RD, 10.0%; 95% CI, 4.5 to 18.9; P < .001). For brisk walking, the 3-year DFS was 81.7% with < 1.0 h/wk and 88.4% with ≥ 3.0 h/wk (RD, 6.7%; 95% CI, 3.0 to 13.8; P < .001). For muscle strengthening activity, the 3-year DFS was 81.8% with 0.0 h/wk and 88.8% for ≥ 0.5 h/wk (RD, 7.0%; 95% CI, 3.1 to 14.2; P = .003). CONCLUSION Among patients with stage III colon cancer enrolled in a trial of postoperative treatment, larger volumes of recreational physical activity, longer durations of light- to moderate-intensity aerobic physical activity, or any vigorous-intensity aerobic physical activity were associated with the greatest improvements in DFS.

Purpose: To investigate the role of pre- and post-stereotactic body radiation therapy (SBRT) neutrophil-to-lymphocyte ratio (NLR) in patients with localized pancreatic cancer treated with anti-PD-1 (programmed cell death protein-1) antibody and SBRT.Materials and Methods: This was a retrospective review of 68 patients with borderline resectable or locally advanced pancreatic cancer treated with anti-PD-1 antibody and SBRT after multi-agent chemotherapy. Immunotherapy was administered with 5-fraction SBRT in the neoadjuvant, concurrent, or adjuvant/maintenance setting. Clinical outcomes included overall survival (OS), local progression-free survival, distant metastasis-free survival, and progression-free survival. Median pre- and post-SBRT peripheral blood markers were compared with the Mann-Whitney U test. Univariate and multivariable analyses (UVA and MVA) were performed to identify variables associated with clinical outcomes. Linear regression was performed to determine correlations between variables and peripheral blood markers. Results: A total of 68 patients were included in the study. The percent change between median pre- and post-SBRT absolute lymphocyte count (ALC), absolute neutrophil count, and NLR were -36.0% (p < 0.001), -5.6% (p = 0.190), and +35.7% (p = 0.003), respectively. Median OS after SBRT was 22.4 months. On UVA, pre-SBRT CA19-9 (hazard ratio [HR] = 1.001; 95% confidence interval [CI], 1.000–1.001; p = 0.031), post-SBRT ALC (HR = 0.33; 95% CI, 0.11–0.91; p = 0.031), and post-SBRT NLR (HR = 1.13; 95% CI, 1.04–1.22; p = 0.009) were associated with OS. On MVA, induction chemotherapy duration (HR = 0.75; 95% CI, 0.57–0.99; p = 0.048) and post-SBRT NLR (HR = 1.14; 95% CI, 1.04–1.23; p = 0.002) predicted for OS. Patients with post-SBRT NLR ≥3.2 had a median OS of 15.6 months versus 27.6 months in patients with post-SBRT NLR

BACKGROUND: To report on a cohort of radiation-naïve patients with pancreatic cancer who developed isolated local recurrence following surgical resection and were subsequently treated with stereotactic body radiation therapy (SBRT). METHODS: Patients with pancreatic cancer who were treated with SBRT for isolated local recurrence after surgical resection were retrospectively reviewed. Clinical outcomes were calculated from completion of SBRT and included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS). Univariate (UVA) analysis was performed to identify variables associated with clinical outcomes. Kaplan-Meier method was used for survival outcomes. Toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: From September 2012 to November 2018, a total of 19 patients with localized pancreatic cancer were treated with SBRT for isolated local recurrence after initial surgical resection. No patients had prior radiation. The median biologically effective dose (BED(10)) was 54.8 Gy (range, 37.5–54.8 Gy). Median OS was 17.1 months, with 6-month and 1-year OS rates of 94.4% and 69.6%, respectively. Nine patients (47.4%) developed local failure after SBRT. Pattern of first failure after SBRT was distant in 7 patients (46.7%), local in 5 patients (33.3%), and synchronous distant and local in 3 patients (20.0%). One patient developed local failure after developing distant disease first. Of the 9 local failures, 3 (33.3%) were out-of-field. Median LPFS was 22.2 months, with 6-month and 1-year LPFS rates of 86.9% and 63.2%, respectively. A BED(10)

The purpose of his study was to report on a cohort of patients managed with nonoperative management (NOM) with a watch-and-wait strategy after achieving complete response (CR) to sequential short-course radiation therapy (SCRT) and consolidation chemotherapy.This was a retrospective study of patients treated SCRT and chemotherapy who achieved a CR and were managed with NOM. Bowel function was assessed with European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30, EORTC Quality of Life Questionnaire-Colorectal Cancer 29, and the low anterior resection syndrome (LARS) questionnaires. Endpoints included overall survival (OS), freedom from local failure (FFLF), freedom from distant metastasis, and disease-free survival (DFS).Twenty-six patients met inclusion criteria. Seven (26.9%) patients developed local failure at a median of 6.8 months following CR, of which 5 were successfully salvaged. Median FFLF was not reached, with 6-month, 1-, and 2-year FFLF rates of 100.0%, 82.3%, and 71.3%. Median OS was not reached, with 6-month, 1-, and 2-year OS rates of 100%. Median DFS was not reached, with 6-month, 1-, and 2-year DFS rates of 100%, 95.0%, and 89.4%. Questionnaire response rate was 83.3%. Median LARS score was 27. Major, minor, and no LARS occurred in 3 (20%), 6 (40%), and 6 (40%) patients, respectively. There were no differences in questionnaire scores between patients who had the majority of their anal sphincter complex irradiated and those who did not.NOM with a watch-and-wait strategy is safe and feasible in patients with locally advanced rectal cancer who achieve CR after sequential SCRT and chemotherapy, with evidence for good anorectal function.

Migrant populations have significant barriers for vocational rehabilitation (VR). Over one-quarter (26%) of farmworkers in the United States are migrant workers. Migrant farmwork often involves exposure to enhanced occupational hazards. Language barriers among farmworkers add additional challenges to vocational rehabilitation, as 77% of U.S. farmworkers identify Spanish as their primary language. Educational attainment is also a factor in vocational development for farmworkers, as the average level of education among farmworkers is eighth grade. Most migrant farmworkers are separated from all nuclear family members. A migratory lifestyle, isolated social conditions, lack of education, language differences, and fear of arrest or deportation establish barriers for VR service. In light of these unique barriers, the first step in improving VR outreach is to determine the geography of migrant work. This study utilizes data from the U.S. Department of Agriculture’s Atlas of Rural and Small-Town America to identify states and counties with the highest rates of Mexican-born residents and highest rates of non-English speakers, discussing that data in the context of unemployment and poverty rates. A State Average Score was developed to arrange states by multiple factors that may indicate the presence of migrant communities. These multiple factors include counties with the highest non-English speaking rates, counties with the highest Mexican-born rates, counties with the highest poverty rates, and counties with the highest unemployment rates. The convergence of these data points within a single county may indicate the presence of migrant communities. Examples of outreach to migrant farmworkers are also presented.

Purpose: The purpose of this study was to determine if somatic mutations are associated with clinical and pathologic outcomes in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) who were treated with neoadjuvant chemotherapy and stereotactic body radiotherapy (SBRT). Materials and Methods: Patients treated with neoadjuvant chemotherapy and SBRT followed by surgical resection from August 2016 to January 2019 and who underwent next generation sequencing of their primary tumor were included in the study. Next-generation sequencing was performed either in-house with a Solid Tumor Panel or with FoundationOne CDx. Univariate (UVA) and multivariable analyses (MVA) were performed to determine associations between somatic mutations and pathologic and clinical outcomes. Results: Thirty-five patients were included in the study. Chemotherapy consisted of modified FOLFIRINOX, gemcitabine and nab-paclitaxel, or gemcitabine and capecitabine. Patients were treated with SBRT in 33 Gy in 5 fractions. On UVA and MVA, tumors with KRAS G12V mutation demonstrated better pathologic tumor regression grade (TRG) to neoadjuvant therapy when compared to tumors with other KRAS mutations (odds ratio = 0.087; 95% confidence interval [CI], 0.009–0.860; p = 0.036). On UVA and MVA, mutations in NOTCH1/2 were associated with worse overall survival (hazard ratio [HR] = 4.15; 95% CI, 1.57–10.95; p = 0.004) and progression-free survival (HR = 3.61; 95% CI, 1.41–9.28; p = 0.008). On UVA, only mutations in NOTCH1/2 were associated with inferior distant metastasis-free survival (HR = 3.38; 95% CI, 1.25–9.16; p = 0.017). Conclusion: In BRPC and LAPC, the KRAS G12V mutation was associated with better TRG following chemotherapy and SBRT. Additionally, NOTCH1/2 mutations were associated with worse overall survival, distant metastasis-free survival, and progression-free survival.

Instructor use of online gamification techniques using platforms such as Kahoot has been increasing in recent years. Prior research has found that the use of gamification can increase student engag...

DNA damage and resulting neoantigen formation is considered a mechanism for synergy between radiotherapy and PD-1/PD-L1 pathway inhibition to induce antitumor immune response. We investigated neoadjuvant chemoradiotherapy (nCRT)-induced changes in CD8+ tumor infiltrating lymphocyte, PD-L1 and mucin expression in rectal cancer patients.Tumor samples of rectal adenocarcinoma patients undergoing resection between 2008-2014 with (PD-L1 expression on TCs was identified in 7.6% (6/79) of nCRT specimens (nCRT exposure was associated with a non-significant difference in PD-L1 expression in rectal adenocarcinoma patients, possibly due to sample size limitations. Further mechanistic investigations and comprehensive immune analysis are needed to understand nCRT-induced immunologic shift in rectal cancer and to expand the applicability of checkpoint inhibitors in this setting.

Customer churn management focuses on identifying potential churners and implementing incentives that can cure churn. The success of a churn management program depends on accurately identifying pote...

BACKGROUND: The purpose of this study is to report on the prognostic role of pre- and post-stereotactic body radiation therapy (SBRT) neutrophil-to-lymphocyte ratio (NLR) in a cohort of patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) who was treated with multi-agent induction chemotherapy followed by five-fraction SBRT. METHODS: Patients treated with multi-agent induction chemotherapy followed by SBRT from August 2016 to January 2019 and who had laboratory values available for review were included in the study. Univariate (UVA) and multivariate analyses (MVA) were performed to determine associations between pre-/post-SBRT NLR and overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS). RESULTS: A total of 156 patients were treated with multi-agent induction chemotherapy followed by SBRT and had laboratory values available for review. On UVA, chemotherapy duration ≥4 months, poorly differentiated disease, inability to undergo resection, pre-SBRT ANC ≥3.7 No./µL, pre-SBRT NLR ≥2.3, and post-SBRT NLR ≥2.6 were associated with worse OS. Patients with post-SBRT NLR ≥2.6 had a median OS of 16.7 months versus median OS not yet reached in patients with post-SBRT

Initial reports supporting the possibility of inflammation in the brain in obsessive-compulsive disorder (OCD) evolved from the models of Sydenham's Chorea, and Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS), which implicated excessive autoimmune responses following exposure to group A B-hemolytic streptococcal infections. Subsequently, this model was expanded to Pediatric Autoimmune Neuropsychiatric Syndrome (PANS) which applied the same concept but included other infections. A critical shortcoming of this model was that it was attributable to a small minority of OCD cases. The relationship between inflammation and OCD was more broadly demonstrated through translocator protein (TSPO) positron emission tomography imaging, a method that detects gliosis, an important component of brain inflammation, in neuropsychiatric diseases, including morphological activation and proliferation of microglia and to some extent astroglia. This method identified greater TSPO binding in the cortico-striatal-thalamo-cortical circuit in OCD, providing a direct brain measure of an important component of inflammation. To identify OCD cases with prominent elevations in TSPO binding in clinical research settings with lower cost peripheral markers, a promising approach is to apply blood serum biomarkers of inflammatory molecules produced by activated microglia and astroglia (gliosis). Such measures may aid stratification in future clinical trials. Several inflammatory-modifying interventions, including celecoxib, minocycline, and n-acetylcysteine, have been tested as treatments in randomized double-blind placebo controlled clinical trials and there is a tendency toward positive results, although these medications are not optimized for brain penetration and sample sizes for most trials were small. Future clinical trials of medications that target gliosis in OCD should apply larger sample sizes, ideally incorporating stratification approaches to enrich samples for the presence of gliosis.

Triaxial induction is a powerful tool to identify thin-bed reservoirs that would be missed with conventional techniques and to improve the accuracy of net pay estimation. On the other hand, it has been noticed that with the standard processing, the resolution of horizontal and vertical resistivities cannot match that of the 2-foot array induction resistivity. Sometimes large apparent anisotropy can be seen in high-resistivity clean sands, which has caused confusion in data interpretation and reserve evaluation. Researchers have long known that triaxial induction data contains high-frequency information from the formation through the abrupt change and spikes of transverse coupling logs near bed boundaries. In this paper, we present a novel pixel inversion equipped with a revamped cost function and a data-driven regularization scheme to better resolve thin beds by using the high-frequency information that had not been used to its full potential. The pixel inversion is a variant of the maximum entropy inversion that has proved to be superior for conventional induction data. However, the direct use of the method for triaxial induction data tends to give a slowly varying vertical resistivity log that fails to resolve thin beds as desired. This issue is resolved by means of two adaptive relaxation terms for the smoothness regularization determined by utilizing the data sensitivity to horizontal and vertical resistivities that evolve continuously with the iteration. In favorable conditions, results on a variety of synthetic models show that a thin bed of less than 1 ft can be detected with deep arrays. In contrast, a bed less than 2 ft can hardly be seen with previous inversions. Results also show that apparent anisotropy ratio is reduced significantly in high-resistivity isotropic cases emulating clean sands. Moreover, the horizontal and vertical resistivities compare favorably with array induction logs in terms of accuracy in the clean sand cases. Field cases confirm that the pixel inversion is clearly superior to the standard triaxial 1D inversion as far as the vertical (or along-hole) resolution is concerned. The thin beds that can now been seen on horizontal and vertical resistivity logs of the pixel inversion are in good agreement with nuclear logs. In the cases of high-resistivity clean sands, the large apparent anisotropy is largely eliminated with the pixel inversion.

American-produced B-29 Superfortress bomber aircraft flew missions against Imperial Japan in the Pacific Theater from air bases in the Mariana Islands from November 1944 until the end of WWII. Mechanical failures forced many B-29s into the ocean surrounding Saipan and Tinian. Terrestrial wreckage of these aircraft has been located in the Pacific region, but no losses in deep water were located until 2016, when a NOAA exploration cruise investigated sonar targets in the Saipan Channel, between Saipan and Tinian. Disarticulated wreckage from a B-29 was located at 370 m over a large area of the seabed. Telepresence-enabled, non-invasive exploration from NOAA Ship Okeanos Explorer allowed scientists on shore to view live streaming video and to work collaboratively to guide the investigation. Experts in aviation archaeology, corrosion studies, WWII history, forensic studies, marine biology, and oceanography participated in the survey using an ROV, highlighting components which could lead to possible identification of the B-29 in situ, and conducting an environmental characterization of the site. This deep-water aircraft site exemplifies multiple-stakeholder driven research in aviation archaeology and highlights several issues in the value of individual site identification.

This article analyzes empirical research in which the sales manager is the unit of analysis to determine what knowledge has been generated by sales scholars about sales managers and sales managemen...

Many companies are increasingly selling hybrid bundles, which comprise one or more goods and one or more services. Hybrid bundle pricing depends on understanding consumer willingness to pay (WTP) for the bundle, which rests on trade-offs among the benefits from four key drivers: service autonomy, complementarity, service quality variability, and overall bundle quality (basic vs. premium). The effects of these drivers and their interactions on the WTP of hybrid bundles are unknown. The authors develop hypotheses and test them rigorously using incentive-aligned choice-based conjoint and hierarchical Bayesian analysis. The results offer important guidelines for developing appropriate hybrid bundles. If a typical firm under budget constraint has to offer either of two hybrid bundles, one with high complementarity or one with service autonomy, the results suggest that it should offer the bundle with high complementarity. Furthermore, contrary to the conventional wisdom of minimizing service quality variability for premium quality bundles relative to basic quality bundles, the results recommend lowering service quality variability for basic quality bundles but maintaining it for premium bundles.

This analysis identifies relationships between library usage, poverty, and median household income in Iowa. Quantitative analysis identifies two distinctive correlations within this data set. First...

Retailers are increasingly offering hybrid bundles—products that combine both good(s) and service(s). Some hybrid bundles, such as Lowe's flooring that combines flooring material (good) and flooring installation (service) are sold in traditional stores, while others, such as Best Buy's bundle that includes a computer (good) and tech support (service) are also offered online. The pricing strategy of a hybrid bundle is critical to its success. While pricing strategies for a goods bundle have been well-studied, those for a services bundle have been underexplored. Hybrid bundles, which fundamentally differ from bundles of goods or bundles of services, primarily with regard to quality variability and scalability, have received even less attention. Drawing from the pricing and bundling literatures for both goods and services, we develop an analytic model of optimal pricing for hybrid bundles by a monopolist retailer. We derive and illustrate many useful propositions, several of which are counter-intuitive. Our results show that an increase in quality variability of the service is associated with a higher optimal hybrid bundle price and a lower optimal price of the good, but a lower overall bundle profit. Our findings also reveal that the optimal price of the service (good) in a hybrid bundle is higher (lower) when the good has diminishing unit cost and the service has constant unit cost (i.e., the good is more scalable than the service). Our results also show that higher unit costs incurred to achieve lower service quality variability can result in higher (lower) profits when the cost increase is low (high). We discuss important implications of these insights for researchers and practitioners.

Purpose When advertising is provided in the form of product placements – the inclusion of branded products within media programming – it can increase or decrease the consumer’s utility. This paper aims to investigate the relationship between product placements and the evaluation of media programming by consumers. The authors hypothesize that consumers do not necessarily consider them as traditional advertising because placements of real brands can enhance realism even if placements sometimes interrupt consumption experience. Thus, the authors believe the relationship between product placements and consumer evaluation is overall positive. However, too many product placements in a single program may reverse this relationship. In addition, the relationship might differ based on the nature of programming, such as art versus entertainment films. Design/methodology/approach Empirical analyses were conducted on 134 movies released between 2000 and 2007 using a generalized method of moments instrumental variable approach. Findings The estimation results from product placement data on 134 movies released between 2000 and 2007 show that product placements have a significant positive effect on consumer ratings, but when used in excess, the effect becomes negative. In addition, a significant interaction exists between the nature of the film (mainstream vs independent) and the number of placements, such that consumers of independent films are much less likely to view product placements positively. Originality/value This research is the first empirical paper that demonstrates the effect of product placements on the evaluation of the media using secondary data.

Estrogen therapy (ET), an effective treatment for perimenopausal depression, often fails to ameliorate symptoms when initiated late after the onset of menopause. Our previous work has suggested that alternative splicing of RNA might mediate these differential effects of ET.Female Sprague–Dawley rats were treated with estradiol (E2) or vehicle 6 days (early ET) or 180 days (late ET) after ovariectomy (OVX). We investigated the differential expression of RNA splicing factors and tryptophan hydroxylase 2 (TPH2) protein using a customized RT2 Profiler PCR Array, reverse-transcription polymerase chain reaction, immunoprecipitation and behaviour changes in clinically relevant early and late ET.Early ET, but not late ET, prolonged swimming time in the forced swim test and reduced anxiety-like behaviours in the elevated plus maze. It reversed OVX-increased (SFRS7 and SFRS16) or OVX-decreased (ZRSR2 and CTNNB1) mRNA levels of splicing factors and ERβ splicing changes in the brains of OVX rats. Early ET, but not late ET, also increased the expression of TPH2 and decreased monoamine oxidase A levels in the dorsal raphe in the brains of OVX rats. In late ET, only diarylpropionitrile (an ERβ-specific agonist) achieved similar results — not E2 (an ERα and ERβ agonist) or propylpyrazoletriol (an ERα-specific agonist).Our experimental paradigm mimicked early and late ET in the clinical setting, but the contribution of age and OVX might be difficult to distinguish.These findings suggest that ERβ alternative splicing and altered responses in the regulatory system for serotonin may mediate the antidepressant efficacy of ET associated with the timing of therapy initiation. It is likely that ERβ-specific ligands would be effective estrogen-based antidepressants late after the onset of menopause.

This study discusses literary and film interests among library patrons in assisted-living residences in a small-town Midwestern context. The importance of library services for seniors is addressed. Popular genres and literary themes are discussed, and the concepts of “relational librarianship” and senior services librarian are advocated. This article attempts to identify popular literary and film genres among seniors living in care facilities for the purpose of enhancing library services for senior citizens.

As a result of high prevalence and high rates of treatment resistance, major depressive disorder has become the leading cause of death and disability in moderate-income to high-income nations. Poor targeting of phenotypes is a plausible reason for treatment resistance and PET imaging offers a unique role to identify phenotypes. Both increased monoamine oxidase A binding and greater translocator protein 18 kDa binding occur throughout the gray matter during major depressive episodes, including affect-modulating brain regions such as the prefrontal and anterior cingulate cortex, and are detectable with advanced radioligand technology for both of these targets.