An Elevated Reservoir of Air Pollutants over the Mid-Atlantic States During the 2011 DISCOVER-AQ Campaign: Airborne Measurements and Numerical Simulations

During a classic heat wave with record high temperatures and poor air quality from July 18 to 23, 2011, an elevated reservoir of air pollutants was observed over and downwind of Baltimore, MD, with relatively clean conditions near the surface. Aircraft and ozonesonde measurements detected approximately 120 parts per billion by volume ozone at 800 meters altitude, but approximately 80 parts per billion by volume ozone near the surface. High concentrations of other pollutants were also observed around the ozone peak: approximately 300 parts per billion by volume CO at 1200 meters, approximately 2 parts per billion by volume NO2 at 800 meters, approximately 5 parts per billion by volume SO2 at 600 meters, and strong aerosol optical scattering (2 x 10 (sup 4) per meter) at 600 meters. These results suggest that the elevated reservoir is a mixture of automobile exhaust (high concentrations of O3, CO, and NO2) and power plant emissions (high SO2 and aerosols). Back trajectory calculations show a local stagnation event before the formation of this elevated reservoir. Forward trajectories suggest an influence on downwind air quality, supported by surface ozone observations on the next day over the downwind PA, NJ and NY area. Meteorological observations from aircraft and ozonesondes show a dramatic veering of wind direction from south to north within the lowest 5000 meters, implying that the development of the elevated reservoir was caused in part by the Chesapeake Bay breeze. Based on in situ observations, Community Air Quality Multi-scale Model (CMAQ) forecast simulations with 12 kilometers resolution overestimated surface ozone concentrations and failed to predict this elevated reservoir; however, CMAQ research simulations with 4 kilometers and 1.33 kilometers resolution more successfully reproduced this event. These results show that high resolution is essential for resolving coastal effects and predicting air quality for cities near major bodies of water such as Baltimore on the Chesapeake Bay and downwind areas in the Northeast

Fitting the integrated Spectral Energy Distributions of Galaxies

Fitting the spectral energy distributions (SEDs) of galaxies is an almost universally used technique that has matured significantly in the last decade. Model predictions and fitting procedures have improved significantly over this time, attempting to keep up with the vastly increased volume and quality of available data. We review here the field of SED fitting, describing the modelling of ultraviolet to infrared galaxy SEDs, the creation of multiwavelength data sets, and the methods used to fit model SEDs to observed galaxy data sets. We touch upon the achievements and challenges in the major ingredients of SED fitting, with a special emphasis on describing the interplay between the quality of the available data, the quality of the available models, and the best fitting technique to use in order to obtain a realistic measurement as well as realistic uncertainties. We conclude that SED fitting can be used effectively to derive a range of physical properties of galaxies, such as redshift, stellar masses, star formation rates, dust masses, and metallicities, with care taken not to over-interpret the available data. Yet there still exist many issues such as estimating the age of the oldest stars in a galaxy, finer details ofdust properties and dust-star geometry, and the influences of poorly understood, luminous stellar types and phases. The challenge for the coming years will be to improve both the models and the observational data sets to resolve these uncertainties. The present review will be made available on an interactive, moderated web page (sedfitting.org), where the community can access and change the text. The intention is to expand the text and keep it up to date over the coming years.Comment: 54 pages, 26 figures, Accepted for publication in Astrophysics & Space Scienc

Abemaciclib in Combination With Endocrine Therapy for Patients With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: A Phase 1b Study

Background Cyclin-dependent kinases (CDK) 4 and 6 regulate G1 to S cell cycle progression and are often altered in cancers. Abemaciclib is a selective inhibitor of CDK4 and CDK6 approved for administration on a continuous dosing schedule as monotherapy or as combination therapy with an aromatase inhibitor or fulvestrant in patients with advanced or metastatic breast cancer. This Phase 1b study evaluated the safety and tolerability, pharmacokinetics, and antitumor activity of abemaciclib in combination with endocrine therapy for metastatic breast cancer (MBC), including aromatase inhibitors (letrozole, anastrozole, or exemestane) or tamoxifen. Patients and Methods Women ≥18 years old with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) MBC were eligible for enrollment. Eligibility included measurable disease or non-measurable but evaluable bone disease by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, Eastern Cooperative Oncology Group performance status 0–1, and no prior chemotherapy for metastatic disease. Adverse events were graded by the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 and tumor response were assessed by RECIST v1.1. Results Sixty-seven patients were enrolled and received abemaciclib 200 mg every 12 hours in combination with letrozole (Part A, n=20), anastrozole (Part B, n=16), tamoxifen (Part C, n=16), or exemestane (Part D, n=15). The most common treatment-emergent adverse events (TEAE) were diarrhea, fatigue, nausea, and abdominal pain. Grade 4 TEAEs were reported in five patients (one each with hyperglycemia, hypertension, neutropenia, procedural hemorrhage, and sepsis). There was no effect of abemaciclib or endocrine therapy on the pharmacokinetics of any combination study drug. Across all treated patients, the median progression-free survival was 25.4 months (95% confidence interval: 18.0, 35.8). The objective response rate was 38.9% in 36 patients with measurable disease. Conclusions Abemaciclib in combination with multiple endocrine therapy options exhibited manageable safety and promising antitumor activity in patients with HR+, HER2- MBC. Clinical Trial Registration https://clinicaltrials.gov/, identifier NCT0205713

In Vivo Assessment of Cold Adaptation in Insect Larvae by Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy

Background Temperatures below the freezing point of water and the ensuing ice crystal formation pose serious challenges to cell structure and function. Consequently, species living in seasonally cold environments have evolved a multitude of strategies to reorganize their cellular architecture and metabolism, and the underlying mechanisms are crucial to our understanding of life. In multicellular organisms, and poikilotherm animals in particular, our knowledge about these processes is almost exclusively due to invasive studies, thereby limiting the range of conclusions that can be drawn about intact living systems. Methodology Given that non-destructive techniques like 1H Magnetic Resonance (MR) imaging and spectroscopy have proven useful for in vivo investigations of a wide range of biological systems, we aimed at evaluating their potential to observe cold adaptations in living insect larvae. Specifically, we chose two cold-hardy insect species that frequently serve as cryobiological model systems–the freeze-avoiding gall moth Epiblema scudderiana and the freeze-tolerant gall fly Eurosta solidaginis. Results In vivo MR images were acquired from autumn-collected larvae at temperatures between 0°C and about -70°C and at spatial resolutions down to 27 µm. These images revealed three-dimensional (3D) larval anatomy at a level of detail currently not in reach of other in vivo techniques. Furthermore, they allowed visualization of the 3D distribution of the remaining liquid water and of the endogenous cryoprotectants at subzero temperatures, and temperature-weighted images of these distributions could be derived. Finally, individual fat body cells and their nuclei could be identified in intact frozen Eurosta larvae. Conclusions These findings suggest that high resolution MR techniques provide for interesting methodological options in comparative cryobiological investigations, especially in vivo

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Engagement and Regulatory Dimensions:A report provided to the Australian Government by the Reef Restoration and Adaptation Program

Social acceptability, effective community engagement and robust regulatory systems are fundamental requirements for the development and future deployment of prospective interventions. These requirements are critical for ensuring the feasibility and viability of any proposed interventions.As such, the critical needs of the Reef Restoration and Adaptation Program (RRAP) include understanding the social acceptability (or otherwise) of proposed interventions or specific technologies; assessing how proposed interventions (or non-intervention) may affect the diverse social and cultural values, uses and benefits associated with the Reef; and identifying appropriate ways to engage different groups and interests in the co-design, deployment and evaluation of proposed interventions or technologies over time. Increasingly, the principles of responsible research and innovation are creating a global impetus for greater levels of public participation in technology research, development and assessment (Stilgoe et al., 2013). When participation builds stakeholder and public trust, understanding and ownership of an initiative, it can lead to increased success or reduced conflict (Reed, 2008). The RRAP will need to adopt engagement processes suited to the general public, to place-based or interest-based stakeholders such as reef communities or reef-dependent industries and with Indigenous Traditional Owners as rights-holders and custodians of the Reef.Results from a nationally representative survey of Australian and Reef region residents conducted during the concept feasibility program indicate there is strong public in-principle support for science-based intervention to restore the Reef and support adaptation. Survey respondents were also generally accepting or undecided about specific technologies, suggesting cautious support exists for specific interventions. The early stage of RRAP, the still hypothetical status of several interventions and limited information available to survey respondents means caution is required in interpreting these results. In-depth interviews with Reef stakeholders (e.g. environmental non-government organisations, tourism organisations and local governments in the Reef catchment) expressed greater levels of uncertainty about the restoration and adaptation technologies and raised concerns about ecological and socio-economic risks. Both stakeholders and Traditional Owners strongly assert that for risks to be identified and managed, and benefits to be realised, meaningful participation and transparency in decision-making and in the research and development (R&D) process is required. There was a widely-held view that restoration-based intervention on the Reef was necessary; however, for many stakeholders,the credibility of RRAP also depended on governments addressing direct threats to the Reefsuch as climate change. The Reef stakeholder engagement and Traditional Owner context is complex and will continue to evolve over the life of the RRAP R&D Program. Engagement strategies tailored to RRAP R&D needs will require detailed planning, co-design, coordination and trials, and the development of novel models of engagement and techniques to support participation and improve overall program performance. The existing Great Barrier Reef regulatory and policy environment as it relates to proposed RRAP interventions is robust, but it was not designed for the current context where significant new threats exist for the Reef. As such, it is no longer entirely fit-for-purpose. The current regulatory framework is complex, fragmented and overlapping. Its capacity to assess novel risks and impacts associated with unconventional interventions is limited. Reef restoration and adaptation interventions pose an unprecedented challenge to the capacity of the existing regulatory system to address novel risks and impacts, in the context of high levels of uncertainty and untested mechanisms for observation and monitoring. The regulatory component of the RRAP R&D Program will work with the relevant regulatory authorities to help inform the development and deployment of a regulatory system that is better able to anticipate and assess the range of risks and impacts associated with unconventional reef restoration and adaptation interventions. Ongoing collaboration with the relevant regulatory bodies will enable the development of an appropriate, fit- for-purpose regulatory framework and policy best practice for reef adaption and restoration.Achieving such a robust and enabling regulatory environment for reef restoration and adaptation will require focus on the following program areas: • Regulatory capacity: identifying short-, medium- and long-term priorities to improve regulatory capacity to address RRAP interventions. • Guidelines and training:preparing guidelines, and delivering training, to RRAP researchers, to ensure they are fully aware of the regulatory environment pertaining to the Great Barrier Reef. • Cooperation between regulators:facilitating further cooperation between the Great Barrier Reef Marine Park Authority and other relevant regulators, with expert input from RRAP scientists on RRAP interventions involving emerging technologies (e.g. genetic engineering and geoengineering). • Permission system: developing options to improve the permission system for reef restoration and adaptation interventions.• Policy and regulatory innovation: developing options for regulatory and policy innovation. • Whole-of-government reef restoration policy: preparing options for whole-of-government reef restoration policy development