Robust Estimation and Inference on Current Status Data with Applications to Phase IV Cancer Trial

The use of piecewise exponential distributions was proposed by Rai et al. (2013) for analyzing cardiotoxicity data. Some parametric models are proposed, but the focus is on the Weibull distribution, which overcomes the limitation of piecewise exponential

Pregnancy-associated cardiomyopathy in survivors of childhood cancer

Current information regarding pregnancy-associated cardiomyopathy among women treated for childhood cancer is insufficient to appropriately guide counseling and patient management. This study aims to characterize its prevalence within a large cohort of females exposed to cardiotoxic therapy

Aromatic Structure in Simulates Titan Aerosol

Observations of Titan by the Cassini Composite Infrared Spectrometer (CIRS) between 560 and 20 per centimeter (approximately 18 to 500 micrometers) have been used to infer the vertical variations of Titan's ice abundances, as well as those of the aerosol from the surface to an altitude of 300 km [1]. The aerosol has a broad emission feature centered approximately at 140 per centimeter (71 micrometers). As seen in Figure 1, this feature cannot be reproduced using currently available optical constants from laboratory-generated Titan aerosol analogs [2]. The far-IR is uniquely qualified for investigating low-energy vibrational motions within the lattice structures of COITIDlex aerosol. The feature observed by CIRS is broad, and does not likely arise from individual molecules, but rather is representative of the skeletal movements of macromolecules. Since Cassini's arrival at Titan, benzene (C6H6) has been detected in the atmosphere at ppm levels as well as ions that may be polycyclic aromatic hydrocarbons (PAHs) [3]. We speculate that the feature may be a blended composite that can be identified with low-energy vibrations of two-dimensional lattice structures of large molecules, such as PAHs or nitrogenated aromatics. Such structures do not dominate the composition of analog materials generated from CH4 and N2 irradiation. We are performing studies forming aerosol analog via UV irradiation of aromatic precursors - specifically C6H6 - to understand how the unique chemical architecture of the products will influence the observable aerosol characteristics. The optical and chemical properties of the aromatic analog will be compared to those formed from CH4/N2 mixtures, with a focus on the as-yet unidentified far-IR absorbance feature. Preliminary results indicate that the photochemically-formed aromatic aerosol has distinct chemical composition, and may incorporate nitrogen either into the ring structure or adjoined chemical groups. These compositional differences are demonstrated in the aerosol mass spectra shown in Figure 2. The aromatic aerosol also demonstrates strong chemical reactivity when exposed to laboratory air, indicating substantial stored chemical potential. Oxidatoin and solubility studies wil be presented and implicatoins for prebiotic chemistry o nTitan will be discussed

Technology-delivered adaptations of motivational interviewing for the prevention and management of chronic diseases: Scoping review

BACKGROUND: Motivational interviewing (MI) can increase health-promoting behaviors and decrease health-damaging behaviors. However, MI is often resource intensive, precluding its use with people with limited financial or time resources. Mobile health-based versions of MI interventions or technology-delivered adaptations of MI (TAMIs) might increase reach. OBJECTIVE: We aimed to understand the characteristics of existing TAMIs. We were particularly interested in the inclusion of people from marginalized sociodemographic groups, whether the TAMI addressed sociocontextual factors, and how behavioral and health outcomes were reported. METHODS: We employed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for scoping reviews to conduct our scoping review. We searched PubMed, CINAHL, and PsycInfo from January 1, 1996, to April 6, 2022, to identify studies that described interventions incorporating MI into a mobile or electronic health platform. For inclusion, the study was required to (1) describe methods/outcomes of an MI intervention, (2) feature an intervention delivered automatically via a mobile or electronic health platform, and (3) report a behavioral or health outcome. The exclusion criteria were (1) publication in a language other than English and (2) description of only in-person intervention delivery (ie, no TAMI). We charted results using Excel (Microsoft Corp). RESULTS: Thirty-four studies reported the use of TAMIs. Sample sizes ranged from 10 to 2069 participants aged 13 to 70 years. Most studies (n=27) directed interventions toward individuals engaging in behaviors that increased chronic disease risk. Most studies (n=22) oversampled individuals from marginalized sociodemographic groups, but few (n=3) were designed specifically with marginalized groups in mind. TAMIs used text messaging (n=8), web-based intervention (n=22), app + text messaging (n=1), and web-based intervention + text messaging (n=3) as delivery platforms. Of the 34 studies, 30 (88%) were randomized controlled trials reporting behavioral and health-related outcomes, 23 of which reported statistically significant improvements in targeted behaviors with TAMI use. TAMIs improved targeted health behaviors in the remaining 4 studies. Moreover, 11 (32%) studies assessed TAMI feasibility, acceptability, or satisfaction, and all rated TAMIs highly in this regard. Among 20 studies with a disproportionately high number of people from marginalized racial or ethnic groups compared with the general US population, 16 (80%) reported increased engagement in health behaviors or better health outcomes. However, no TAMIs included elements that addressed sociocontextual influences on behavior or health outcomes. CONCLUSIONS: Our findings suggest that TAMIs may improve some health promotion and disease management behaviors. However, few TAMIs were designed specifically for people from marginalized sociodemographic groups, and none included elements to help address sociocontextual challenges. Research is needed to determine how TAMIs affect individual health outcomes and how to incorporate elements that address sociocontextual factors, and to identify the best practices for implementing TAMIs into clinical practice

Sex-based differences in functional brain activity during working memory in survivors of pediatric acute lymphoblastic leukemia

BACKGROUND: Long-term survivors of pediatric acute lymphoblastic leukemia are at elevated risk for neurocognitive deficits and corresponding brain dysfunction. This study examined sex-based differences in functional neuroimaging outcomes in acute lymphoblastic leukemia survivors treated with chemotherapy alone. METHODS: Functional magnetic resonance imaging (fMRI) and neurocognitive testing were obtained in 123 survivors (46% male; median [min-max] age = 14.2 years [8.3-26.5 years]; time since diagnosis = 7.7 years [5.1-12.5 years]) treated on the St. Jude Total XV treatment protocol. Participants performed the n-back working memory task in a 3 T scanner. Functional neuroimaging data were processed (realigned, slice time corrected, normalized, smoothed) and analyzed using statistical parametric mapping with contrasts for 1-back and 2-back conditions, which reflect varying degrees of working memory and task load. Group-level fMRI contrasts were stratified by sex and adjusted for age and methotrexate exposure. Statistical tests were 2-sided (P \u3c .05 statistical significance threshold). RESULTS: Relative to males, female survivors exhibited less activation (ie, reduced blood oxygen dependent-level signals) in the right parietal operculum, supramarginal gyrus and inferior occipital gyrus, and bilateral superior frontal medial gyrus during increased working memory load (family-wise error-corrected P = .004 to .008, adjusting for age and methotrexate dose). Female survivors were slower to correctly respond to the 2-back condition than males (P \u3c .05), though there were no differences in overall accuracy. Performance accuracy was negatively correlated with fMRI activity in female survivors (Pearson\u27s r = -0.39 to -0.29, P = .001 to .02), but not in males. CONCLUSIONS: These results suggest the working memory network is more impaired in female survivors than male survivors, which may contribute to ongoing functional deficits

Baker Center Journal of Applied Public Policy, Vol. I No. I

Welcome to the first issue of the Baker Center Journal of Applied Public Policy. Throughout my many years of service, I always have been impressed with the tremendous good that can be accomplished through the creation and implementation of sound public policy. I hope that, along the way, I have contributed to the body of policies that help our nation function in a strong, effective, compassionate, and prosperous fashion. As we launch this new Journal, under the auspices of the Howard H. Baker Jr. Center for Public Policy at the University of Tennnnessee, I wanted to briefly expand on some of the reasons I believe that this journal is necessary and why I believe that research on public policy is so vitally important. This Journal aims to discuss applied public policy. The goal is not to engage in theoretical discussions, though I believe those are important. Instead, we hope that the Baker Journal will focus on the most current issues that directly affect our nation and our world on the operational, or mechanical level. We intend to engage a wide variety of contributors. Scholars, of course, will be asked to write on critical topics of research. We also aim to include contributions from those who draft, approve and execute public policy at the local, state, and national levels. Additionally, at least one article in each issue will be reserved for the work of a university-level student. Our approach is varied, and I know that the result will be an intellectually sound and extraordinarily interesting presentation of experiences and ideas.I am especially pleased that so many University of Tennnnessee students are involved in the formulation and operation of the Journal. Our editorial board is comprised of some of the University of Tennnnessee’s most promising undergraduate, graduate, and law school students. With dedicated assistance and oversight from faculty and from the Baker Center, this board of extraordinarily intelligent and committed students has worked very hard to make this Journal a reality. The Center has also formed a national advisory panel for the Journal. I am a member of that panel, and I must note that I am grateful for the involvement and support of my colleagues who have agreed to serve with me: Ms. Emily Reynolds, former Secretary of the United States Senate; Congressman Bob Clement, former Tennnnessee Congressman; Mr. Glennnn Reynolds, noted author and professor of law at the University of Tennnnessee; Dr. Joseph Cooper, an accomplished professor of political science at Johns Hopkins University; and Mr. John Seigenthaler, distinguished journalist and founder and director of the First Amendment Center at Vanderbilt University. I believe it is critical that we think deeply about the issues that are confronting us today. Our representative system of governance is based on an informed citizenry and informed public servants. From international issues such as the war on terror and energy challenges to more local but equally important topics such as sustainable development and education, we must commit ourselves to understanding all challenges free of partisan rhetoric. Only then can we confront them together. It is my hope that this Journal will add to that understanding and will speak to many audiences. From the classroom to the boardroom, from city hall to the halls of our legislatures, I believe the work put forward in our journal will be useful for everyone who wants to be informed and engaged. It is an exciting undertaking, and I thank you for your support

Reproductive function and outcomes in female survivors of childhood, adolescent and young adult cancer: a review

Some survivors of childhood, adolescent, and young adult cancer are at increased risk of gonadal dysfunction and adverse pregnancy outcomes. We reviewed currently available literature that evaluated reproductive function and pregnancy outcomes of female cancer survivors diagnosed before the age of 25 years. High-dose alkylating agent chemotherapy and abdominal/pelvic radiotherapy adversely affect gonadal function in a dose-related fashion, with older age at exposure conferring greater risk as a result of the age-related decline in ovarian reserve. Gonadal injury clinically manifests as ovarian hormone insufficiency (delayed or arrested puberty, premature ovarian insufficiency, or premature menopause) and infertility. The effect of molecular-targeted agents on ovarian function has not been established. For female cancer survivors who maintain fertility, overall pregnancy (relative risk, 0.67 to 0.81) and live birth rates (hazard ratio, 0.79 to 0.82) are lower than those in the general public. Pregnancy in cancer survivors also may be associated with risks to both the mother and the fetus related to miscarriage; preterm birth; and, rarely, cardiomyopathy. Women at risk for these complications require preconception assessment and counseling from both obstetricians and oncology providers. The risk for inherited genetic disease in offspring conceived after cancer treatment exposure is not increased. The optimization of reproductive outcomes and minimization of risks of pregnancy complications in survivors requires informed, risk-based assessment and monitoring

Cytotoxic T Lymphocyte Therapy for Epstein-Barr Virus+ Hodgkin's Disease

Epstein Barr virus (EBV)+ Hodgkin's disease (HD) expresses clearly identified tumor antigens derived from the virus and could, in principle, be a target for adoptive immunotherapy with viral antigen–specific T cells. However, like most tumor-associated antigens in immunocompetent hosts, these potential targets are only weakly immunogenic, consisting primarily of the latent membrane protein (LMP)1 and LMP2 antigens. Moreover, Hodgkin tumors possess a range of tumor evasion strategies. Therefore, the likely value of immunotherapy with EBV-specific cytotoxic effector cells has been questioned. We have now used a combination of gene marking, tetramer, and functional analyses to track the fate and assess the activity of EBV cytotoxic T lymphocyte (CTL) lines administered to 14 patients treated for relapsed EBV+ HD. Gene marking studies showed that infused effector cells could further expand by several logs in vivo, contribute to the memory pool (persisting up to 12 mo), and traffic to tumor sites. Tetramer and functional analyses showed that T cells reactive with the tumor-associated antigen LMP2 were present in the infused lines, expanded in peripheral blood after infusion, and also entered tumor. Viral load decreased, demonstrating the biologic activity of the infused CTLs. Clinically, EBV CTLs were well tolerated, could control type B symptoms (fever, night sweats, and weight loss), and had antitumor activity. After CTL infusion, five patients were in complete remission at up to 40 mo, two of whom had clearly measurable tumor at the time of treatment. One additional patient had a partial response, and five had stable disease. The performance and fate of these human tumor antigen–specific T cells in vivo suggests that they might be of value for the treatment of EBV+ Hodgkin lymphoma

Intronic Non-CG DNA hydroxymethylation and alternative mRNA splicing in honey bees

Abstract Background Previous whole-genome shotgun bisulfite sequencing experiments showed that DNA cytosine methylation in the honey bee (Apis mellifera) is almost exclusively at CG dinucleotides in exons. However, the most commonly used method, bisulfite sequencing, cannot distinguish 5-methylcytosine from 5-hydroxymethylcytosine, an oxidized form of 5-methylcytosine that is catalyzed by the TET family of dioxygenases. Furthermore, some analysis software programs under-represent non-CG DNA methylation and hydryoxymethylation for a variety of reasons. Therefore, we used an unbiased analysis of bisulfite sequencing data combined with molecular and bioinformatics approaches to distinguish 5-methylcytosine from 5-hydroxymethylcytosine. By doing this, we have performed the first whole genome analyses of DNA modifications at non-CG sites in honey bees and correlated the effects of these DNA modifications on gene expression and alternative mRNA splicing. Results We confirmed, using unbiased analyses of whole-genome shotgun bisulfite sequencing (BS-seq) data, with both new data and published data, the previous finding that CG DNA methylation is enriched in exons in honey bees. However, we also found evidence that cytosine methylation and hydroxymethylation at non-CG sites is enriched in introns. Using antibodies against 5-hydroxmethylcytosine, we confirmed that DNA hydroxymethylation at non-CG sites is enriched in introns. Additionally, using a new technique, Pvu-seq (which employs the enzyme PvuRts1l to digest DNA at 5-hydroxymethylcytosine sites followed by next-generation DNA sequencing), we further confirmed that hydroxymethylation is enriched in introns at non-CG sites. Conclusions Cytosine hydroxymethylation at non-CG sites might have more functional significance than previously appreciated, and in honey bees these modifications might be related to the regulation of alternative mRNA splicing by defining the locations of the introns