High Time for Conservation: Adding the Environment to the Debate on Marijuana Liberalization

The liberalization of marijuana policies, including the legalization of medical and recreational marijuana, is sweeping the United States and other countries. Marijuana cultivation can have significant negative collateral effects on the environment that are often unknown or overlooked. Focusing on the state of California, where by some estimates 60% -- 70% of the marijuana consumed in the United States is grown, we argue that (a) the environmental harm caused by marijuana cultivation merits a direct policy response, (b) current approaches to governing the environmental effects are inadequate, and (c) neglecting discussion of the environmental impacts of cultivation when shaping future marijuana use and possession policies represents a missed opportunity to reduce, regulate, and mitigate environmental harm

Use and Protection of GPS Sidelobe Signals for Enhanced Navigation Performance in High Earth Orbit

The application of the Global Positioning System (GPS) for navigation of spacecraft in High and Geosynchronous Earth Orbit (HEO/GEO) has crossed a threshold and is now being employed in operational missions. Utilizing advanced GPS receivers optimized for these missions, space users have made extensive use of the sidelobe transmissions from the GPS satellites to realize navigation performance that far exceeds that predicted by pre-launch simulations. Unfortunately, the official specification for the GPS Space Service Volume (SSV), developed in 2006, assumes that only signals emanating from the main beam of the GPS transmit antenna are useful for navigation, which greatly under-estimates the number of signals available for navigation purposes. As a result, future high-altitude space users may be vulnerable to any GPS design changes that suppress the sidelobe transmissions, beginning with Block III space vehicles (SVs) 11-32. This paper presents proposed changes to the GPS system SSV requirements, as informed by data from recent experiments in the SSV and new mission applications that are enabled by GPS navigation in HEO/GEO regimes. The NASA/NOAA GOES-R series satellites are highlighted as an example of a mission that relies on this currently-unspecified GPS system performance to meet mission requirements

Before the Flood: Impact of Coordination of Care and Direct Admissions on Emergency Department Volumes

Background: Transfers of pediatric patients occur to access specialty and subspecialty care, but incur risk, and consume resources. Direct admissions to medical and surgical wards may improve patient experience and mitigate resource utilization. Objective: We sought to identify common elements for direct admissions, as well as the pattern of disposition for patients referred to our emergency department (ED). Design: A retrospective qualitative analysis of patients transferred to our pediatric hospital for 12 months was performed. Different physician groups were evaluated for use of direct admissions or evaluation in the ED. Patients referred to the ED were additionally tracked to evaluate their eventual disposition. Results: A total of 3982 transfers occurred during the 12-month analysis period. Of those, 3463 resulted in admission, accounting for 32.55% of all admissions. Transfers accepted by nonsurgical services accounted for 82% of the transfers, whereas 18% were facilitated by one of the surgical services. Direct admissions accounted for 1707 (44.8%) of all referrals and were used more often by nonsurgical services. Of patients referred to the ED (2101 or 55.2% of all referrals), most patients were admitted and 343 (16% of those referred to the ED) were discharged home. Conclusions: The direct admission process helped avoid ED assessments for some patients; however, some patients referred to the ED were able to be evaluated, treated, and discharged. Consistent triage of the patients being transferred as direct admissions may improve ED throughput and potentially improve the patient's experience, reduce redundant services, and expedite care

The ADVANCE network: accelerating data value across a national community health center network

The ADVANCE (Accelerating Data Value Across a National Community Health Center Network) clinical data research network (CDRN) is led by the OCHIN Community Health Information Network in partnership with Health Choice Network and Fenway Health. The ADVANCE CDRN will ‘horizontally’ integrate outpatient electronic health record data for over one million federally qualified health center patients, and ‘vertically’ integrate hospital, health plan, and community data for these patients, often under-represented in research studies. Patient investigators, community investigators, and academic investigators with diverse expertise will work together to meet project goals related to data integration, patient engagement and recruitment, and the development of streamlined regulatory policies. By enhancing the data and research infrastructure of participating organizations, the ADVANCE CDRN will serve as a ‘community laboratory’ for including disadvantaged and vulnerable patients in patient-centered outcomes research that is aligned with the priorities of patients, clinics, and communities in our network

Use and Protection of GPS Sidelobe Signals for Enhanced Navigation Performance in High Earth Orbit

GPS (Global Positioning System) Space Service Volume (SSV) signal environment is from 3,000-36,000 kilometers altitude. Current SSV specifications only capture performance provided by signals transmitted within 23.5(L1) or 26(L2-L5) off-nadir angle. Recent on-orbit data lessons learned show significant PNT (Positioning, Navigation and Timing) performance improvements when the full aggregate signal is used. Numerous military civil operational missions in High Geosynchronous Earth Orbit (HEOGEO) utilize the full signal to enhance vehicle PNT performanc

Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.

Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires

Diversification and speciation among Laurentian brachiopods during the GOBE: insights from basinal and regional analyses

Full understanding of diversity dynamics during the Great Ordovician Biodiversification Event (GOBE) requires analyses that investigate regional and species-level data and patterns. In this study, we combine bedding-plane scale data on brachiopod species counts and shell size col­lected from the Simpson Group of Oklahoma, USA, with species-level phylogenetic biogeography for three articulated brachiopod lineages that occurred throughout Laurentia. From these data, we ascertain that the primary influences of brachiopod shell size and diversity in the Simpson Group reflect global drivers, notably temporal position and paleotemperature. Similarly, the primary speciation pattern observed within Hesperorthis, Mimella, and Oepikina is the oscillation in speciation mode between dispersal and vicariance, which reflect the connection and disconnection of geographic areas, respectively. Processes that facilitate cyclical connectivity are global to regional in scale such as oceanographic changes, glacial cycles, or tectonic pulses. Therefore, both regional and continental scale analyses reinforce the importance of global factors in driving diversification during the GOBE

Variable Stars in Leo A: RR Lyraes, Short-period Cepheids, and Implications on Stellar Content

We present the results of a search for short-period variable stars in Leo A. We have found 92 candidate variables, including eight candidate RR Lyrae stars. From the RR Lyraes, we measure a distance modulus of (m-M)_0 = 24.51 +/- 0.12, or 0.80 +/- 0.04 Mpc. This discovery of RR Lyraes confirms, for the first time, the presence of an ancient (> ~11 Gyr) population in Leo A accounting for at least 0.1% of the galaxy's V luminosity. We have also discovered a halo of old (> ~2 Gyr) stars surrounding Leo A, with a scale length roughly 50% larger than that of the dominant young population. We also report the discovery of a large population of Cepheids in Leo A. The median absolute magnitude of our Cepheid sample is M_V = -1.1, fainter than 96% of SMC and 99% of LMC Cepheids. Their periods are also unusual, with three Cepheids that are deduced to be pulsating in the fundamental mode having periods of under 1 day. Upon examination, these characteristics of the Leo A Cepheid population appear to be a natural extension of the classical Cepheid period-luminosity relations to low metallicity, rather than being indicative of a large population of ``anomalous'' Cepheids. We demonstrate that the periods and luminosities are consistent with the expected values of low-metallicity blue helium-burning stars (BHeBs), which populate the instability strip at lower luminosities than do higher-metallicity BHeBs.Comment: 46 pages, 12 figures Accepted by A

An actionable anti-racism plan for geoscience organizations.

Geoscience organizations shape the discipline. They influence attitudes and expectations, set standards, and provide benefits to their members. Today, racism and discrimination limit the participation of, and promote hostility towards, members of minoritized groups within these critical geoscience spaces. This is particularly harmful for Black, Indigenous, and other people of color in geoscience and is further exacerbated along other axes of marginalization, including disability status and gender identity. Here we present a twenty-point anti-racism plan that organizations can implement to build an inclusive, equitable and accessible geoscience community. Enacting it will combat racism, discrimination, and the harassment of all members

Unexpected Noncovalent Off-Target Activity of Clinical BTK Inhibitors Leads to Discovery of a Dual NUDT5/14 Antagonist

Cofactor mimicry represents an attractive strategy for the development of enzyme inhibitors but can lead to off-target effects due to the evolutionary conservation of binding sites across the proteome. Here, we uncover the ADP-ribose (ADPr) hydrolase NUDT5 as an unexpected, noncovalent, off-target of clinical BTK inhibitors. Using a combination of biochemical, biophysical, and intact cell NanoBRET assays as well as X-ray crystallography, we confirm catalytic inhibition and cellular target engagement of NUDT5 and reveal an unusual binding mode that is independent of the reactive acrylamide warhead. Further investigation of the prototypical BTK inhibitor ibrutinib also revealed potent inhibition of the largely unstudied NUDIX hydrolase family member NUDT14. By exploring structure–activity relationships (SARs) around the core scaffold, we identify a potent, noncovalent, and cell-active dual NUDT5/14 inhibitor. Cocrystallization experiments yielded new insights into the NUDT14 hydrolase active site architecture and inhibitor binding, thus providing a basis for future chemical probe design