Anthropometric risk factors for ovarian cancer in the NIH-AARP diet and health study

OBJECTIVE Identifying potentially modifiable risk factors for ovarian cancer is essential for prevention because this cancer is predominantly detected at a late stage. Here, we estimated the relations of general adiposity and measures reflecting body fat distribution to the risk of epithelial ovarian cancer. METHODS We ascertained 683 ovarian epithelial cancers (343 high-grade serous, 141 non-high grade serous) among 145,575 women, aged 50-72 years (median follow-up 12.6 years), from the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. Using Cox models, we estimated confounder-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for associations of overall ovarian cancer, high-grade serous and non-high-grade serous carcinoma with body mass index, waist circumference, hip circumference, waist-hip ratio, waist-height ratio, body adiposity index, body shape index, and abdominal volume index. RESULTS Anthropometric measures were unrelated to overall ovarian cancer, high-grade serous cancer, and non-high-grade serous cancer. For example, the HR for overall ovarian cancer per standard deviation increment of body mass index at baseline was 0.98 (95% CI 0.88-1.10). Similar associations were observed with measurements of body fat distribution. CONCLUSION These results do not indicate that adult adiposity is associated with ovarian cancer risk in post-menopausal women

Multi-Disciplinary Project-Based Paradigm That Uses Hands-On Desktop Learning Modules and modern Learning Pedagogies

It has been established that traditional lectures ARE NOT best for student learning – yet that is what the community almost universally does! Furthermore, engineers work in broad multidisciplinary teams while classroom learning is individual and narrow. Yet, educators rarely invest the time and resources necessary to employ such innovations. In this CCLI type II award we are further refining Desktop Learning Modules (DLMs) within a Cooperative, Hands-on, Active, Problem based, Learning (CHAPL) setting for Chemical, Civil, Mechanical, Bio- and Electrical Engineering courses at a diverse set of institutions, including a community college engaged through a distance learning mode. A workbook is being developed and tested for easier adoption of the hands-on units and accompanying pedagogy. Existing concept inventories are not always showing significant gains in apparent student learning either for control or experimental groups and we are concluding these assessments are not well aligned with the macroscale design calculations being emphasized in the course. Therefore, new concept question assessments are being developed consisting of some macroscale questions from past inventories along with conceptual essay and calculation based questions aligned more specifically with the DLM processes at hand. Past implementations like this show students learn key concepts at least as well from each other in a guided inquiry as they do from lecture. Also, a mixed qualitative / quantitative assessment using a critical reasoning rubric reveals student abilities become better aligned with what is expected of graduating engineers ready for industry and that the CHAPL/DLM environment serves to reinforce understanding of physical phenomena, and to develop analytical and evaluative problem-solving skills. Interviews, surveys and team reports reveal students are better able to visualize concepts and that classroom exercises are promoting team skills and academic rigor. Faculty interviews reveal enhanced awareness of student misconceptions and improved monitoring of student growth in conceptual understanding and interpersonal skills. The poster and paper will highlight our findings and illustrate the CHAPL environment. Hands-on DLMs with cartridges used in teaching principles in the various disciplines will be demonstrated. A survey will be offered to those viewing the poster to assess potential interest in adoption of the DLMs and in participating in a follow-on NSF Type III proposal for Transforming Undergraduate Engineering Education through use of the DLMs and associated CHAPL pedagogies

Gene Expression Profile and Acute Gene Expression Response to Sclerostin Inhibition in Osteogenesis Imperfecta Bone

Sclerostin antibody (SclAb) therapy has been suggested as a novel therapeutic approach toward addressing the fragility phenotypic of osteogenesis imperfecta (OI). Observations of cellular and transcriptional responses to SclAb in OI have been limited to mouse models of the disorder, leaving a paucity of data on the human OI osteoblastic cellular response to the treatment. Here, we explore factors associated with response to SclAb therapy in vitro and in a novel xenograft model using OI bone tissue derived from pediatric patients. Bone isolates (approximately 2 mm3) from OI patients (OI type III, type III/IV, and type IV, n = 7; non‐OI control, n = 5) were collected to media, randomly assigned to an untreated (UN), low‐dose SclAb (TRL, 2.5 μg/mL), or high‐dose SclAb (TRH, 25 μg/mL) group, and maintained in vitro at 37°C. Treatment occurred on days 2 and 4 and was removed on day 5 for TaqMan qPCR analysis of genes related to the Wnt pathway. A subset of bone was implanted s.c. into an athymic mouse, representing our xenograft model, and treated (25 mg/kg s.c. 2×/week for 2/4 weeks). Implanted OI bone was evaluated using μCT and histomorphometry. Expression of Wnt/Wnt‐related targets varied among untreated OI bone isolates. When treated with SclAb, OI bone showed an upregulation in osteoblast and osteoblast progenitor markers, which was heterogeneous across tissue. Interestingly, the greatest magnitude of response generally corresponded to samples with low untreated expression of progenitor markers. Conversely, samples with high untreated expression of these markers showed a lower response to treatment. in vivo implanted OI bone showed a bone‐forming response to SclAb via μCT, which was corroborated by histomorphometry. SclAb induced downstream Wnt targets WISP1 and TWIST1, and elicited a compensatory response in Wnt inhibitors SOST and DKK1 in OI bone with the greatest magnitude from OI cortical bone. Understanding patients’ genetic, cellular, and morphological bone phenotypes may play an important role in predicting treatment response. This information may aid in clinical decision‐making for pharmacological interventions designed to address fragility in OI. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156449/2/jbm410377_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156449/1/jbm410377.pd

Mental health and health-related quality of life in preschool-aged childhood cancer survivors : results of the prospective cohort study ikidS-OEVA

Objectives Long-term survivors of childhood cancer are at increased risk for sequelae such as poor mental health (MH) or impaired health-related quality of life (HrQoL). We aimed to evaluate early adverse effects on MH and HrQoL in young childhood cancer survivors (YCCS) before school entry. Methods In a nationwide prospective cohort study, children with cancer other than brain tumors diagnosed at preschool age and completed cancer treatments were identified from the German Childhood Cancer Registry. The comparison group was children of the same age without a cancer diagnosis who participated in the prospective population-based health survey ikidS. MH problems and HrQoL were assessed by parental versions of the Strengths and Difficulties Questionnaire (SDQ) and the questionnaire for health-related quality of life in children (KINDL), respectively. Associations between cancer and MH as well as HrQoL were analyzed by multivariable linear regression. Results Of 382 YCCS contacted, 145 were enrolled (mean age 6.6 years) and 124 analyzed. Compared to children without a cancer diagnosis (3683 contacted, 2003 enrolled, 1422 analyzed), YCCS had more MH problems (13% vs. 3%) and slightly worse HrQoL (median 78.7 vs. 80.2 points). In the adjusted analysis, YCCS had higher SDQ scores (2.2 points, 95% confidence interval [CI] 1.3, 3.0) and lower KINDL scores (−2.4 points, 95% CI −3.7, −1.1) compared to children without cancer diagnosis. Conclusion Already at preschool age, YCCS may be at increased risk of MH problems and impaired HrQoL. This could have impacts on subsequent school performance and educational attainment. Follow-up health care for YCCS may include early screening for MH problems and reasons for HrQoL deficits

Nonpromoter methylation of the CDKN2A gene with active transcription is associated with improved locoregional control in laryngeal squamous cell carcinoma

We previously reported a novel association between CDKN2A nonpromoter methylation and transcription (ARF/INK4a) in human papillomavirus associated oropharyngeal tumors. In this study we assessed whether nonpromoter CDKN2A methylation in laryngeal squamous cell carcinomas (LXSCC) conferred a similar association with transcription that predicted patient outcome. We compared DNA methylation and ARF/INK4a RNA expression levels for the CDKN2A locus using the Illumina HumanMethylation27 beadchip and RT-PCR in 43 LXSCC tumor samples collected from a prospective study of head and neck cancer patients treated at Montefiore Medical Center (MMC). Validation was performed using RNAseq data on 111 LXSCC tumor samples from the Cancer Genome Atlas (TCGA). The clinical relevance of combined nonpromoter CDKN2A methylation and transcription was assessed by multivariate Cox regression for locoregional recurrence on a subset of 69 LXSCC patients with complete clinicopathologic data from the MMC and TCGA cohorts. We found evidence of CDKN2A nonpromoter hypermethylation in a third of LXSCC from our MMC cohort, which was significantly associated with increased ARF and INK4a RNA expression (Wilcoxon rank-sum, P = 0.007 and 0.003, respectively). A similar association was confirmed in TCGA samples (Wilcoxon rank-sum test P < 0.0001 for ARF and INK4a). Patients with CDKN2A hypermethylation or high ARF/INK4a expression were significantly less likely to develop a locoregional recurrence compared to those with neither of the features, independent of other clinicopatholgic risk factors (adjusted hazard ratio=0.21, 95% confidence interval:0.05-0.81). These results support the conclusion that CDKN2A nonpromoter methylation is associated with increased ARF and INK4a RNA expression, and improved locoregional control in LXSCC

Herschel observations of deuterated water towards Sgr B2(M)

Observations of HDO are an important complement for studies of water, because they give strong constraints on the formation processes -- grain surfaces versus energetic process in the gas phase, e.g. in shocks. The HIFI observations of multiple transitions of HDO in Sgr~B2(M) presented here allow the determination of the HDO abundance throughout the envelope, which has not been possible before with ground-based observations only. The abundance structure has been modeled with the spherical Monte Carlo radiative transfer code RATRAN, which also takes radiative pumping by continuum emission from dust into account. The modeling reveals that the abundance of HDO rises steeply with temperature from a low abundance ($2.5\times 10^{-11}$) in the outer envelope at temperatures below 100~K through a medium abundance ($1.5\times 10^{-9}$) in the inner envelope/outer core, at temperatures between 100 and 200~K, and finally a high abundance ($3.5\times 10^{-9}$) at temperatures above 200~K in the hot core.Comment: A&A HIFI special issue, accepte

Development of 200-GHz to 2.7-THz multiplier chains for submillimeter-wave heterodyne receivers

Several astrophysics and Earth observation space missions planned for the near future will require submillimeter-wave heterodyne radiometers for spectral line observations. One of these, the Far InfraRed and Submillimeter Telescope will perform high-sensitivity, high-resolution spectroscopy in the 400 to 2700 GHz range with a seven channel super- conducting heterodyne receiver complement. The local oscillators for all these channels will be constructed around state-of-the-art GaAs power amplifiers in the 71 to 115 GHz range, followed by planar Schottky diode multiplier chains. The Jet Propulsion Laboratory is responsible for developing the multiplier chains for the 1.2, 1.7, and 2.7 THz bands. This paper will focus on the designs and technologies being developed to enhance the current state- of-the-art, which is based on discrete planar or whisker contacted GaAs Schottky diode chips mounted in waveguide blocks. We are proposing a number of new planar integrated circuit and device topologies to implement multipliers at these high frequencies. Approaches include substrateless, framed and frameless GaAs membrane circuitry with single, and multiple planar integrated Schottky diodes. Circuits discussed include 200 and 400 GHz doublers, a 1.2 THz tripler and a 2.4 THz doubler. Progress to date, with the implications of this technology development for future Earth and space science instruments, is presented

Opening the black box of energy modelling: Strategies and lessons learned

The global energy system is undergoing a major transition, and in energy planning and decision-making across governments, industry and academia, models play a crucial role. Because of their policy relevance and contested nature, the transparency and open availability of energy models and data are of particular importance. Here we provide a practical how-to guide based on the collective experience of members of the Open Energy Modelling Initiative (Openmod). We discuss key steps to consider when opening code and data, including determining intellectual property ownership, choosing a licence and appropriate modelling languages, distributing code and data, and providing support and building communities. After illustrating these decisions with examples and lessons learned from the community, we conclude that even though individual researchers' choices are important, institutional changes are still also necessary for more openness and transparency in energy research

All-Solid-State 2.45-to-2.78-THz Source

Sources in the THz range are required in order for NASA to implement heterodyne instruments in this frequency range. The source that has been demonstrated here will be used for an instrument on the SOFIA platform as well as for upcoming astrophysics missions. There are currently no electronic sources in the 2 3- THz frequency range. An electronically tunable compact source in this frequency range is needed for lab spectroscopy as well as for compact space-deployable heterodyne receivers. This solution for obtaining useful power levels in the 2 3- THz range is based on utilizing power-combined multiplier stages. Utilizing power combining, the input power can be distributed between different multiplier chips and then recombined after the frequency multiplication. A continuous wave (CW) coherent source covering 2.48 2.75 THz, with greater than 10 percent instantaneous and tuning bandwidth, and having l 14 W of output power at room temperature, has been demonstrated. This source is based on a 91.8 101.8-GHz synthesizer followed by a power amplifier and three cascaded frequency triplers. It demonstrates that purely electronic solid-state sources can generate a useful amount of power in a region of the electromagnetic spectrum where lasers (solid-state or gas) were previously the only available coherent sources. The bandwidth, agility, and operability of this THz source has enabled wideband, high-resolution spectroscopic measurements of water, methanol, and carbon monoxide with a resolution and signal-to-noise ratio unmatched by other existing systems, providing new insight in the physics of these molecules. Further - more, the power and optical beam quality are high enough to observe the Lamb-dip effect in water. The source frequency has an absolute accuracy better than 1 part in 1012, and the spectrometer achieves sub-Doppler frequency resolution better than 1 part in 108. The harmonic purity is better than 25 dB. This source can serve as a local oscillator for a variety of heterodyne systems, and can be used as a method for precision control of more powerful but much less frequency-agile quantum mechanical terahertz sources