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For some students enrolled in online courses, receiving tutoring may be a key component to their success. This study sought to determine if the use of an outsourced online tutoring service (OOTS) was associated with course success in online English Composition courses. The authors employed chi-square tests to analyze the relationship between tutoring usage and final grades for students in two different composition courses, English Composition I (n = 888) and English Composition II (n = 1108). The results indicate that in both courses, students who utilized the OOTS passed the course at higher rates than those who did not. For students who utilized the service at least once, 95% passed English Composition I, compared with a 57% passing rate of students who did not utilize the service. Results for English Composition II were similar with 89% of OOTS users passing the course, compared with a 58% passing rate of non-users. This research supports and discusses the importance of online tutoring for students.

Introduction: Immunotherapies such as checkpoint blockade, have demonstrated remarkable clinical efficacy yet a large percentage of patients do not respond, potentially due to a paucity of pre-existing immune priming against neoantigens. We developed a personalized genome vaccine (PGV_001) platform to generate neoantigen vaccines targeting each patient’s unique mutanome. Primary objectives of the study were to determine 1) the safety and tolerability; 2) the feasibility of PGV_001 production and administration; and 3) the immunogenicity of PGV_001. Secondary objectives included immunophenotyping vaccine driven cellular and soluble immune milieu in peripheral blood. We previously reported on the clinical efficacy, and here we report, analysis of vaccine-driven immune responses in all treated patients. Methods: The study (Trial Registration NCT02721043) enrolled patients with resected malignancies, including Head and neck squamous cell carcinomas, breast cancer and bladder cancer, or, in the case of multiple myeloma treated with autologous stem cell transplant; all patients determined to have a high risk of disease recurrence (>30% over 5 years). Tumor-derived and germline RNA and DNA was sequenced to predict neoantigens utilizing our custom computation pipeline, OpenVax. Approximately 10 peptides were synthesized per patient, and a mixture of these peptides was administered as 10 subcutaneous and intradermal vaccines over 27 weeks in combination with poly-ICLC and helper Tetanus peptide as adjuvants. Immune responses were analyzed utilizing assays including IFN-gamma ELISPOT, antigen specific T cell expansion followed by flow cytometry, etc. Results: In total 148 neoantigen peptides were manufactured for 15 patients. Overall, 136 PGV_001 doses were administered to 13 patients. Vaccine-specific T cell immunity was observed against multiple vaccine neoepitopes in all 13 subjects. Of the peptides administered, 45% of vaccine antigens (57/126) induced de novo immunity, starting as early as Week8 and often sustaining past last vaccination. Notably, while the vaccine driven T cell immunity was CD4 T cell dominant, most evaluated subjects also displayed vaccine induced polyfunctional CD8-T cell responses. Additional studies are ongoing to define qualities of reactive T cells, evaluate vaccine-induced humoral responses and probe the circulating inflammatory immune milieu. These will be presented. Conclusions: We have established a platform for generating personalized neoantigen vaccines. 100% of the vaccinated patients developed an immune response specific to the vaccine neoantigens predicted by OpenVax. Subjects who received treatment experienced mild Grade 1 or 2 adverse reactions as per the CTEP v 4.0 NCI CTCAE. This vaccine trial reached the primary endpoint of safety, tolerability, feasibility and immunogenicity. Based on the PGV_001 platform two clinical trials, one in patients with glioblastoma multiforme (NCT03223103) in combination with TT fields and second in patients with urothelial carcinoma (NCT03359239) in combination with Atezolizumab have been performed. Data from these trials is under evaluation. Citation Format: Mansi Saxena, Thomas Marron, Julia Kodysh, Alex Rubinsteyn, John Finnigan, Ana Blasquez, Marcia Meseck, Tim O'Donnell, Daniela Delbeau, Mathew Galsky, Deborah Doroshow, Brett Miles, Krzysztof Misiukiewicz, Hanna Irie, Amy Tiersten, Samir Parekh, Marshall Posner, Andrea Wolf, John Mandeli, Rachel Brody, Sacha Gnjatic, Eric Schadt, Philip Friedlander, Nina Bhardwaj. Immunogenicity of PGV_001 neoantigen vaccine in a Phase-I clinical trial, across various types of cancers in adjuvant setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT270.

Human papillomavirus (HPV) is responsible for a growing proportion of oropharyngeal squamous cell carcinomas (OPSCCs) among men and White individuals. Whether similar trends apply to women, non-Whites, and non-oropharyngeal squamous cell carcinomas (non-OPSCCs) is unknown.This is a cross-sectional analysis combining 2 multi-institutional case series of incident head and neck squamous cell carcinoma (HNSCC) cases. Incident HNSCCs from 1995 to 2012 were enrolled retrospectively using banked tumor samples and medical record abstraction. Incident HNSCCs from 2013 to 2019 were enrolled prospectively. The prevalence of tumor HPV biomarkers was tested over 3 time periods (1995-2003, 2004-2012, and 2013-2019). Centralized testing was done for p16 immunohistochemistry (p16) and oncogenic HPV in situ hybridization (ISH).A total of 1209 incident cases of HNSCC were included. Prevalence of p16- and ISH-positive tumors increased significantly for oropharynx cancers over time. The majority were positive after 2013 for White patients (p16, 92%; P .001; ISH 94%; P .001), Black patients (p16, 72%; P = .021; ISH 67%; P = .011), and Hispanic patients (p16, 100%; P = .04; ISH 100%; P = .013). For women with OPSCC, the prevalence of p16- and ISH-positive tumors increased significantly to 82% (P .001) and 78% (P = .004), respectively. For non-OPSCCs, there was increased p16 and ISH positivity overall with 24% p16 and 16% ISH positivity in the most recent time period (P .001 for both).The majority of OPSCCs in US tertiary care centers are now p16 and ISH positive for all sex and race groups. In some populations in the United States, 91% of OPSCCs are now caused by HPV. Few non-OPSCCs are p16 and ISH positive.

Summary The role of oncoviral genotype and co-infection driving oncogenesis remains unclear. We have developed a scalable, high throughput tool for sensitive and precise oncoviral genotype deconvolution. Using tumor RNA sequencing data, we applied it to 537 virally infected liver, cervical, and head and neck tumors, providing the first comprehensive integrative landscape of tumor-viral gene expression, viral antigen immunogenicity, patient survival, and mutational profiling organized by tumor oncoviral genotype. We find that HBV and HPV genotype and co-infection serve as significant predictors of patient survival and immune activation. Finally, we demonstrate that HPV genotype is more associated with viral oncogene expression than cancer type, implying that expression may be similar across episomal and stochastic integration-based infections. While oncoviral infections are known risk factors for oncogenesis, viral genotype and co-infection are shown to strongly associate with disease progression, patient survival, mutational signatures, and putative tumor neoantigen immunogenicity, facilitating novel clinical associations with infections., Graphical abstract, Highlights • ViralMine parses oncoviral genotypes and co-infection from in situ tumor data • Oncoviral genotyping of TCGA CESC, HNSC, and LIHC cohorts • Tumor fitness, immunogenicity, and mutational signatures associate with oncoviral genotype, Genomics; Virology; Cancer

We compared the clinical outcomes and toxicity profile among a retrospective cohort of patients with primary major salivary gland carcinomas (SGCs) treated with surgery followed by adjuvant radiation therapy (S+RT) versus surgery and adjuvant chemoradiotherapy (S+CRT).Twenty patients (71%) underwent S+RT and eight (29%) S+CRT at our Institution between 2006 and 2015. Microscopic positive margins were present in 54% of the patients.The 3-year overall survival (OS) was 100% with S+RT and 87.5% with S+CRT (p=0.141) and locoregional control (LRC) was 95% with S+RT and 87.5% with S+CRT (p=0.383). There were no significant differences in the rate of acute (p=0.801) and late (p=0.714) toxicities.While we await randomized data, adjuvant CRT may be considered as a viable therapeutic option for patients at high-risk of local or regional recurrence, especially in those with a positive microscopic margin where further surgery may result in functional cranial neuropathies.

The purpose of this study was to characterize oncologic outcomes in early (T1-T2, N0) and intermediate (T1-T2, N1) oropharyngeal squamous cell carcinoma (SCC) after surgery.Patients with oropharyngeal SCC treated with surgery were identified from 2 academic institutions.Of 188 patients, 143 met the inclusion criteria. Eighty-six (60%) had T1 to T2 N0 and 57 (40%) had T1 to T2 N1 disease. Sixty-five patients (45%) underwent a robotic-assisted resection, whereas the remaining had transoral (n = 60; 42%), mandible-splitting (n = 11; 8%), or transhyoid approaches (n = 7; 5%). Human papillomavirus (HPV) status was known for 97 patients (68%), and 54 (55%) were HPV positive. Three-year recurrence-free survival (RFS) was 82% (95% confidence interval [CI] = 0.75-0.89). Since 2008, HPV infection was protective of recurrence (log-rank p = .0334). A single node did not increase the risk of recurrence (p = .467) or chance of a second primary (p = .175).Complete surgical resection is effective therapy for early and intermediate oropharyngeal SCC. HPV-negative patients were at increased risk for locoregional recurrence or second primary disease. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1471, 2016.

There is much concern regarding the genesis of acidic leachate by mine tailings and its potential impact on local water systems. Genesis of the leachate and its subsequent escape into the surrounding watershed is controlled by the primary distribution of facies within the tailings pond. Leachate generation and percolation is enhanced in high-sulphide coarse-grained sands, while percolation is restricted in fine-grained clays formed from bentonitic slimes. The Kidd Copper deposit, located on the South Range of the Sudbury Basin, was a typical offset dike nickel deposit, where mining took place between 1970 and 1990. Using a sequence of temporally separate aerial photographs dating from 1945 to 2002, it is possible to document the initial development of the mine, its closure and the subsequent degradation of the mine tailings waste that was produced during mining activity. Since the mine's closure, the resulting tailings deposit has progressively oxidized, generating acid-rich leachate. Leachate can escape from the tailings via surface run-off and subsurface flow. The spatial distribution of possible flow pathways was mapped using a combination of sub-centimetre-resolution real-time kinematic RTK GPS and individual, high-resolution, oriented photographs of subsurface pits. Lithologic mapping information of the Kidd Copper tailings deposit can provide an insight into the distribution of local aquifers and aquitards. Subsurface lithologic mapping was achieved using a combination of sub-centimetre-resolution RTK GPS and individual, high-resolution, oriented photographs of subsurface pits. The photograph of each pit provides lithologic information of a specific point in the tailings deposit, while the high-resolution GPS locates the individual photographs in three-dimensional 3D geographic space. Combining these data allows us to identify continuous lithologic surfaces between pits, leading to the construction of a 3D model of the deposition of the tailings pond. Grain size and textural details extracted from the images of each lithology permit discrimination between aquifers and aquitards. The final geometric model could be used as input for estimating the hydrologic and chemical evolution of the tailings.

An impact event always creates a cloud of ejecta generated through excavation of the target. Subsequent in-filling of the void by crater-fill deposits provides a record of post-impact processes. Full-core digital photographic scans of core segments from borehole LB-07 in the Bosumtwi impact crater provide a complete record of the in-fill process. The shape, orientation, and size of clasts within the impact breccia were measured using a best-fit ellipsoid approach. Clast size and variance, together with clast orientation data, suggest the impact breccias at Bosumtwi can be divided into a simple two-fold subdivision that loosely agrees with the lithological zonation of a lower monomict breccia overlain by a polymict breccia. The lower unit is characterized by a uniform and finer-grained clast size together with a uniform flat-lying clast orientation. The boundary between the two zones is defined by a sharp increase in clast size. The upper zone shows an average increase in clast size with decreasing depth, but full grain size spectrum together with increased grain size deviation suggest that this is a result of mixing between two populations with different grain size distribution. The main population of clasts shows an incremental decrease of clast size with decreasing depth. The upper zone also contains weakly defined shallowly dipping clast fabrics, which may be suggestive of horizontal transport or deposition onto an inclined surface.

The Bosumtwi impact structure in Ghana is the youngest and best-preserved medium-sized impact structure on Earth, and because of the vast amount of prior geophysical and geological data gathered in the area, it constitutes a great natural laboratory to try to develop new geophysical interpretation and modeling techniques. During the 2004 International Continental Scientific Drilling Program (ICDP) drilling campaign at highlight of this study is that we demonstrate that is possible to acquire at least partial vector data with readily available instrumentation.

Although the prognostic role of human papillomavirus (HPV) in locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) is well established, its prognostic and/or predictive role in recurrent/metastatic settings remains to be defined. Despite epidemic growth of HPV-positive oropharyngeal carcinoma, a low recurrence rate in HPV-positive patients results in a small number of patients entering clinical trials for recurrent and/or metastatic SCCHN. The consequent lack of statistical power and also significant data contamination by misclassification of HPV-positive patients leads to premature study conclusions. Even emerging data from the analysis of 2 randomized trials, SPECTRUM and EXTREME, do not provide enough evidence for any HPV-based therapeutic strategy. Many upcoming studies for locally advanced disease, including the ones with de-escalated strategies, will have an increasing number of patients with HPV. Optimal HPV testing strategies for reliable patient selection and HPV-driven therapeutic approaches will be essential. Here, we comprehensively review the existing data regarding HPV status and prognostic or predictive outcomes in recurrent/metastatic settings and discuss current promising studies and future directions that may help in the design of upcoming trials.

Objectives To identify independent predictors of outcome in patients with adenoid cystic carcinoma (ACC) of the paranasal sinuses and skull base. Design Meta-analysis of the literature and data from the International ACC Study Group. Setting University-affiliated medical center. Participants The study group consisted of 520 patients, 99 of them from the international cohort. The median follow-up period was 60 months (range, 32 to 100 months). Main Outcome Measures Overall survival (OS) and disease-specific survival (DSS). Results The 5-year OS and DSS of the entire cohort were 62% and 67%, respectively. The local recurrence rate was 36.6%, and the regional recurrence rate was 7%. Distant metastasis, most commonly present in the lung, was recorded in 106 patients (29.1%). In the international cohort, positive margins and ACC of the sphenoid or ethmoidal sinuses were significant predictors of outcome (p

Adenoid cystic carcinoma (ACC) is a locally aggressive tumor with a high prevalence of distant metastases. The purpose of this study was to identify independent predictors of outcome and to characterize the patterns of failure.An international retrospective review was conducted of 489 patients with ACC treated between 1985 and 2011 in 9 cancer centers worldwide.Five-year overall-survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were 76%, 80%, and 68%, respectively. Independent predictors of OS and DSS were: age, site, N classification, and presence of distant metastases. N classification, age, and bone invasion were associated with DFS on multivariate analysis. Age, tumor site, orbital invasion, and N classification were independent predictors of distant metastases.The clinical course of ACC is slow but persistent. Paranasal sinus origin is associated with the lowest distant metastases rate but with the poorest outcome. These prognostic estimates should be considered when tailoring treatment for patients with ACC.

The purpose of this study was to evaluate the efficacy of preoperative versus intraoperative mandibular contouring using rapid prototyping technology.Ten patients requiring mandibular reconstruction had a preoperative mandibular plate contoured to a fabricated 3D mandibular model based on preoperative imaging. A traditional intraoperative plate was also contoured. Two surgeons blinded to the study compared the plates with respect to conformance, surface-area contact, and best overall match. A cost-benefit analysis was then performed.The average time to contour was 867 ± 243 seconds and 833 ± 289 seconds for the preoperative and intraoperative plates, respectively (p = .83). Interobserver analysis revealed no statistically significant differences in conformance (p = .38) or surface area contact (p = .14). In 7 of 9 cases, the preoperative plate was selected for the final reconstruction. In 1 case, an intraoperative plate was not contoured because of the lateral extent of the tumor.In cases of mandibular distortion secondary to disease, pathologic fracture or defects involving multiple mandibular subsites this method is particularly advantageous.

It was shown previously that houseflies in fast-food restaurants commonly carry antibiotic-resistant and potentially virulent enterococci. In this study, the potential of field-collected houseflies to contaminate ready-to-eat (RTE) food with enterococci was assessed by laboratory bioassays. Houseflies were collected with a sweep net in a cattle feedlot and exposed in groups of 5, 10, 20, and 40 to a beef patty (from an RTE hamburger) for 0.5, 1.0, 3.0, and 24 h. The exposure of RTE food to flies resulted in 100% contamination with enterococci in all bioassays, regardless of the number of houseflies and the length of exposure time. In addition, with the increasing number of houseflies as well as with the increasing time exposure, the concentration of enterococci in RTE food increased. Even a short time exposure (0.5 h) resulted in food contamination, ranging from 3.1 x 10(3) CFU/g (5 houseflies) to 8.4 x 10(4) CFU/g (40 houseflies). The analysis of 23 randomly selected enterococcal isolates from RTE food after the fly exposure revealed a single species, Enterococcus faecalis. In contrast, four Enterococcus species, including E. faecalis (57.1%), E. gallinarum (19.1%), E. hirae (14.3%), and E. faecium (9.5%), represented 21 randomly selected and identified isolates from houseflies. Phenotypic screening showed that E. faecalis isolates from RTE food were resistant to ciprofloxacin (17.4%), tetracycline (13.0%), erythromycin (13.0%), and chloramphenicol (4.3%). This study demonstrates a great potential of houseflies from a cattle feedlot to contaminate RTE food with enterococci in a short time.