Metastatic model of HPV+ oropharyngeal squamous cell carcinoma demonstrates heterogeneity in tumor metastasis

Human papillomavirus induced (HPV+) cancer incidence is rapidly rising, comprising 60–80% of oropharyngeal squamous cell carcinomas (OPSCCs); while rare, recurrent/metastatic disease accounts for nearly all related deaths. An in vivo pre-clinical model for these invasive cancers is necessary for testing new therapies. We characterize an immune competent recurrent/metastatic HPV+ murine model of OPSSC which consists of four lung metastatic (MLM) cell lines isolated from an animal with HPV+ OPSCC that failed cisplatin/radiation treatment. These individual metastatic clonal cell lines were tested to verify their origin (parental transgene expression and define their physiological properties: proliferation, metastatic potential, heterogeneity and sensitivity/resistance to cisplatin and radiation. All MLMs retain expression of parental HPV16 E6 and E7 and degrade P53 yet are heterogeneous from one another and from the parental cell line as defined by Illumina expression microarray. Consistent with this, reverse phase protein array defines differences in protein expression/activation between MLMs as well as the parental line. While in vitro growth rates of MLMs are slower than the parental line, in vivo growth of MLM clones is greatly enhanced. Moreover, in vivo resistance to standard therapies is dramatically increased in 3 of the 4 MLMs. Lymphatic and/or lung metastasis occurs 100% of the time in one MLM line. This recurrent/metastatic model of HPV+ OPSCC retains the characteristics evident in refractory human disease (heterogeneity, resistance to therapy, metastasis in lymph nodes/lungs) thus serving as an ideal translational system to test novel therapeutics. Moreover, this system may provide insights into the molecular mechanisms of metastasis

Structural Forecasting for Short-term Tropical Cyclone Intensity Guidance

Because geostationary satellite (Geo) imagery provides a high temporal resolution window into tropical cyclone (TC) behavior, we investigate the viability of its application to short-term probabilistic forecasts of TC convective structure to subsequently predict TC intensity. Here, we present a prototype model which is trained solely on two inputs: Geo infrared imagery leading up to the synoptic time of interest and intensity estimates up to 6 hours prior to that time. To estimate future TC structure, we compute cloud-top temperature radial profiles from infrared imagery and then simulate the evolution of an ensemble of those profiles over the subsequent 12 hours by applying a Deep Autoregressive Generative Model (PixelSNAIL). To forecast TC intensities at hours 6 and 12, we input operational intensity estimates up to the current time (0 h) and simulated future radial profiles up to +12 h into a ``nowcasting'' convolutional neural network. We limit our inputs to demonstrate the viability of our approach and to enable quantification of value added by the observed and simulated future radial profiles beyond operational intensity estimates alone. Our prototype model achieves a marginally higher error than the National Hurricane Center's official forecasts despite excluding environmental factors, such as vertical wind shear and sea surface temperature. We also demonstrate that it is possible to reasonably predict short-term evolution of TC convective structure via radial profiles from Geo infrared imagery, resulting in interpretable structural forecasts that may be valuable for TC operational guidance

The effects of a workplace intervention on employees’ cortisol awakening response

Work-related stressors are known to adversely affect employees’ stress physiology, including the cortisol awakening response (CAR)–or the spike in cortisol levels shortly after people wake up that aids in mobilizing energy. A flat or blunted CAR has been linked to chronic stress and burnout. This daily diary study tested the effects of a workplace intervention on employed parents’ CAR. Specifically, we tested whether the effects of the intervention on CAR were moderated by the type of days (workday versus non-work day). Data came from 94 employed parents from an information technology firm who participated in the baseline and 12-month diurnal cortisol components of the Work, Family, and Health Study, a group-randomized field experiment. The workplace intervention was designed to reduce work-family conflict (WFC) and implemented after the baseline data collection. Diurnal salivary cortisol was collected on 4 days at both baseline and 12 months. Multilevel modeling revealed that the intervention significantly increased employees’ CAR at 12 months on non-workdays, but this was not evident on workdays or for employees in the usual practice condition. The results provide evidence that the intervention was effective in enhancing employees’ biological stress physiology particularly during opportunities for recovery that are more likely to occur on non-work days.National Institute on Aging (U01AG027669)Work, Family & Health Network (U01HD051217)Work, Family & Health Network (U01HD051218)Work, Family & Health Network (U01HD051256)Work, Family & Health Network (U01HD051276)U.S. Army Research Institute for the Behavioral and Social SciencesNational Institute for Occupational Safety and Health (U010H008788)Alfred P. Sloan Foundation (2004-12-4)William T. Grant Foundation (9844)National Institutes of Health (U.S.) (Penn State General Clinical Research Center. Grant M01-RR-10732

Strategic and Interactive Writing Instruction: An efficacy study in grades 3-5

A quasi-experimental study was conducted to examine the impact of Strategic and Interactive Writing Instruction on 3rd-5th grade deaf and hard of hearing students’ writing and language compared to a business-as-usual condition (N=63). A total of 18 hours of instruction was provided for each of two types of writing—personal narrative (known as recount) and persuasive. Writing samples, collected prior to instruction and after, were scored for writing traits, language accuracy and complexity. Data were analyzed using a two-level, mixed-effects regression. Results show the treatment to be effective for recount and persuasive writing traits, and recount language variables, with effect sizes ranging from 0.46 to 2.01. Treatment effects were also substantial for persuasive writing language outcomes (0.38 to 1.06), although not all were statistically significant at the 0.05 level. The findings suggest the importance of apprenticeship in writing and consideration for the specific language needs of students with hearing loss

The Fine Line Between Normal and Starburst Galaxies

Recent literature suggests that there are two modes through which galaxies grow their stellar mass - a normal mode characterized by quasi-steady star formation, and a highly efficient starburst mode possibly triggered by stochastic events such as galaxy mergers. While these differences are established for extreme cases, the population of galaxies in-between these two regimes is poorly studied and it is not clear where the transition between these two modes of star formation occurs. We utilize ALMA observations of the CO J=3-2 line luminosity in a sample of 20 infrared luminous galaxies that lie in the intermediate range between normal and starburst galaxies at z ~ 0.25-0.6 in the COSMOS field to examine the gas content and star formation efficiency of these galaxies. We compare these quantities to the galaxies' deviation from the well-studied "main sequence" correlation between star formation rate and stellar mass (MS) and find that at log($SFR/SFR_{MS}$) < 0.6, a galaxy's distance to the main sequence is mostly driven by increased gas content, and not a more efficient star formation process.Comment: 21 pages, 10 figure

Hot topics, urgent priorities, and ensuring success for racial/ethnic minority young investigators in academic pediatrics.

BackgroundThe number of racial/ethnic minority children will exceed the number of white children in the USA by 2018. Although 38% of Americans are minorities, only 12% of pediatricians, 5% of medical-school faculty, and 3% of medical-school professors are minorities. Furthermore, only 5% of all R01 applications for National Institutes of Health grants are from African-American, Latino, and American Indian investigators. Prompted by the persistent lack of diversity in the pediatric and biomedical research workforces, the Academic Pediatric Association Research in Academic Pediatrics Initiative on Diversity (RAPID) was initiated in 2012. RAPID targets applicants who are members of an underrepresented minority group (URM), disabled, or from a socially, culturally, economically, or educationally disadvantaged background. The program, which consists of both a research project and career and leadership development activities, includes an annual career-development and leadership conference which is open to any resident, fellow, or junior faculty member from an URM, disabled, or disadvantaged background who is interested in a career in academic general pediatrics.MethodsAs part of the annual RAPID conference, a Hot Topic Session is held in which the young investigators spend several hours developing a list of hot topics on the most useful faculty and career-development issues. These hot topics are then posed in the form of six "burning questions" to the RAPID National Advisory Committee (comprised of accomplished, nationally recognized senior investigators who are seasoned mentors), the RAPID Director and Co-Director, and the keynote speaker.Results/conclusionsThe six compelling questions posed by the 10 young investigators-along with the responses of the senior conference leadership-provide a unique resource and "survival guide" for ensuring the academic success and optimal career development of young investigators in academic pediatrics from diverse backgrounds. A rich conversation ensued on the topics addressed, consisting of negotiating for protected research time, career trajectories as academic institutions move away from an emphasis on tenure-track positions, how "non-academic" products fit into career development, racism and discrimination in academic medicine and how to address them, coping with isolation as a minority faculty member, and how best to mentor the next generation of academic physicians

Phytoplankton blooms weakly influence the cloud forming ability of sea spray aerosol

After many field studies, the establishment of connections between marine microbiological processes, sea spray aerosol (SSA) composition, and cloud condensation nuclei (CCN) has remained an elusive challenge. In this study, we induced algae blooms to probe how complex changes in seawater composition impact the ability of nascent SSA to act as CCN, quantified by using the apparent hygroscopicity parameter (κapp). Throughout all blooms, κapp ranged between 0.7 and 1.4 (average 0.95 ± 0.15), consistent with laboratory investigations using algae‐produced organic matter, but differing from climate model parameterizations and in situ SSA generation studies. The size distribution of nascent SSA dictates that changes in κapp associated with biological processing induce less than 3% change in expected CCN concentrations for typical marine cloud supersaturations. The insignificant effect of hygroscopicity on CCN concentrations suggests that the SSA production flux and/or secondary aerosol chemistry may be more important factors linking ocean biogeochemistry and marine clouds.Key PointsChanges in seawater and sea spray composition did not strongly affect expected CCN concentrationsBlooms may impact clouds more strongly through changes in aerosol flux or secondary chemistryModel parameterizations likely overestimate changes in cloud nuclei due to primary marine organicsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134444/1/grl54978_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134444/2/grl54978-sup-0001-supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134444/3/grl54978.pd