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Background: Ceftolozane/tazobactam (C/T) is a novel cephalosporin/β-lactamase inhibitor currently dosed by 8-hour intervals to treat complicated and multidrug-resistant Pseudomonas aeruginosa infections in inpatients. This dosing strategy limits the ability to transition patients to outpatient antimicrobial therapy. There are limited data in the literature to support continuous infusion (CI) dosing., Methods: This study is a retrospective chart review of patients who received CI C/T at an infusion center part of a community health system. Patients were evaluated from August 2016 through January 2018. Patients were included in the study if they were ≥18 years old and received their entire course of C/T as a CI in the outpatient setting. Patients were excluded if they received any part of their therapy as an inpatient., Results: The primary outcome evaluated was symptom resolution. Secondary outcomes evaluated were microbiologic resolution as well as patient satisfaction. Seven patients received either 4.5 or 9 grams of continuous infusion C/T every 24 hours in the outpatient setting over the study period. For the primary outcome, 6 of 7 patients had symptom resolution. For the secondary outcomes, 3 of 3 patients had microbiologic resolution, and patient satisfaction scores were overall positive among respondents., Conclusions: Ceftolozane/tazobactam delivered as a continuous infusion may be a safe, effective, and convenient way to treat infections caused by P aeruginosa . This novel treatment regimen can be an option for patients to avoid hospital admission or discharge to complete therapy as an outpatient., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Arctic lakes located in permafrost regions are susceptible to catastrophic drainage. In this study, we reconstructed historical lake drainage events on the western Arctic Coastal Plain of Alaska between 1955 and 2017 using USGS topographic maps, historical aerial photography (1955), and Landsat Imagery (ca. 1975, ca. 2000, and annually since 2000). We identified 98 lakes larger than 10 ha that partially (>25% of area) or completely drained during the 62-year period. Decadal-scale lake drainage rates progressively declined from 2.0 lakes/yr (1955-1975), to 1.6 lakes/yr (1975-2000), and to 1.2 lakes/yr (2000-2017) in the ~30,000-km 2 study area. Detailed Landsat trend analysis between 2000 and 2017 identified two years, 2004 and 2006, with a cluster (five or more) of lake drainages probably associated with bank overtopping or headward erosion. To identify future potential lake drainages, we combined the historical lake drainage observations with a geospatial dataset describing lake elevation, hydrologic connectivity, and adjacent lake margin topographic gradients developed with a 5-m-resolution digital surface model. We identified ~1900 lakes likely to be prone to drainage in the future. Of the 20 lakes that drained in the most recent study period, 85% were identified in this future lake drainage potential dataset. Our assessment of historical lake drainage magnitude, mechanisms and pathways, and identification of potential future lake drainages provides insights into how arctic lowland landscapes may change and evolve in the coming decades to centuries., (© 2020 The Authors Permafrost and Periglacial Processes Published by John Wiley & Sons Ltd.)

Introduction: Knowledge in infectious diseases (ID) pharmacotherapy and antimicrobial stewardship is becoming increasingly important for pharmacists. Pharmacy schools utilize multiple methods to teach ID pharmacotherapy including advanced pharmacy practice experiences (APPEs)., Methods: An internet-based survey was sent to students currently on APPEs at four colleges/schools of pharmacy. The primary study objective was a comparison of self-perceived ID knowledge and confidence prior to starting and during APPEs. The secondary objectives were to determine the level of self-perceived knowledge and confidence of students who have completed an ID APPE to those who have not, as well as the level of interest in postgraduate year 1 (PGY-1) and ID-specific postgraduate year 2 (PGY-2) residencies., Results: All statements revealed a statistically significant increase in self-perceived ID knowledge and confidence for students during APPEs compared to before starting rotations (p-values < 0.001). Students who completed an ID APPE had an overall increase in both self-perceived knowledge and confidence for all aspects. Completion of an ID APPE enhanced self-perceived knowledge in basic microbiology fundamentals, antimicrobial stewardship principles, and overall ID knowledge. Completion of an ID APPE created a higher level of confidence regarding selecting appropriate antimicrobial therapy, interpreting cultures and susceptibilities to de-escalate, and communicating with other healthcare professionals., Conclusions: Students who completed an ID APPE had a higher level of self-perceived knowledge and confidence than those who had not. Recent increases in demand for antimicrobial stewardship positions warrants maximization of ID and non-ID APPEs to enhance students' knowledge and confidence in infectious diseases., (Copyright © 2019 Elsevier Inc. All rights reserved.)

With an increasing number of antimicrobial stewardship-related articles published each year, attempting to stay current is challenging. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related peer-reviewed literature that detailed an actionable intervention for 2018. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight the actionable intervention used by antimicrobial stewardship programs to provide key stewardship literature for teaching and training as well as to identify potential intervention opportunities within one's institution., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The evolutionary origins of eusociality represent increases in complexity from individual to caste-based, group reproduction. These behavioural transitions have been hypothesized to go hand in hand with an increased ability to regulate when and where genes are expressed. Bees have convergently evolved eusociality up to five times, providing a framework to test this hypothesis. To examine potential links between putative gene regulatory elements and social evolution, we compare alignable, non-coding sequences in 11 diverse bee species, encompassing three independent origins of reproductive division of labour and two elaborations of eusocial complexity. We find that rates of evolution in a number of non-coding sequences correlate with key social transitions in bees. Interestingly, while we find little evidence for convergent rate changes associated with independent origins of social behaviour, a number of molecular pathways exhibit convergent rate changes in conjunction with subsequent elaborations of social organization. We also present evidence that many novel non-coding regions may have been recruited alongside the origin of sociality in corbiculate bees; these loci could represent gene regulatory elements associated with division of labour within this group. Thus, our findings are consistent with the hypothesis that gene regulatory innovations are associated with the evolution of eusociality and illustrate how a thorough examination of both coding and non-coding sequence can provide a more complete understanding of the molecular mechanisms underlying behavioural evolution. This article is part of the theme issue 'Convergent evolution in the genomics era: new insights and directions'.

Thermokarst lake landscapes are permafrost regions, which are prone to rapid (on seasonal to decadal time scales) changes, affecting carbon and nitrogen cycles. However, there is a high degree of uncertainty related to the balance between carbon and nitrogen cycling and storage. We collected 12 permafrost soil cores from six drained thermokarst lake basins (DTLBs) along a chronosequence north of Teshekpuk Lake in northern Alaska and analyzed them for carbon and nitrogen contents. For comparison, we included three lacustrine cores from an adjacent thermokarst lake and one soil core from a non thermokarst affected remnant upland. This allowed to calculate the carbon and nitrogen stocks of the three primary landscape units (DTLB, lake, and upland), to reconstruct the landscape history, and to analyze the effect of thermokarst lake formation and drainage on carbon and nitrogen stocks. We show that carbon and nitrogen contents and the carbon-nitrogen ratio are considerably lower in sediments of extant lakes than in the DTLB or upland cores indicating degradation of carbon during thermokarst lake formation. However, we found similar amounts of total carbon and nitrogen stocks due to the higher density of lacustrine sediments caused by the lack of ground ice compared to DTLB sediments. In addition, the radiocarbon-based landscape chronology for the past 7,000 years reveals five successive lake stages of partially, spatially overlapping DTLBs in the study region, reflecting the dynamic nature of ice-rich permafrost deposits. With this study, we highlight the importance to include these dynamic landscapes in future permafrost carbon feedback models.

Alkali bees ( Nomia melanderi ) are solitary relatives of the halictine bees, which have become an important model for the evolution of social behavior, but for which few solitary comparisons exist. These ground-nesting bees defend their developing offspring against pathogens and predators, and thus exhibit some of the key traits that preceded insect sociality. Alkali bees are also efficient native pollinators of alfalfa seed, which is a crop of major economic value in the United States. We sequenced, assembled, and annotated a high-quality draft genome of 299.6 Mbp for this species. Repetitive content makes up more than one-third of this genome, and previously uncharacterized transposable elements are the most abundant type of repetitive DNA. We predicted 10,847 protein coding genes, and identify 479 of these undergoing positive directional selection with the use of population genetic analysis based on low-coverage whole genome sequencing of 19 individuals. We found evidence of recent population bottlenecks, but no significant evidence of population structure. We also identify 45 genes enriched for protein translation and folding, transcriptional regulation, and triglyceride metabolism evolving slower in alkali bees compared to other halictid bees. These resources will be useful for future studies of bee comparative genomics and pollinator health research., (Copyright © 2019 Kapheim et al.)

Contemporary climate change in Alaska has resulted in amplified rates of press and pulse disturbances that drive ecosystem change with significant consequences for socio-environmental systems. Despite the vulnerability of Arctic and boreal landscapes to change, little has been done to characterize landscape change and associated drivers across northern high-latitude ecosystems. Here we characterize the historical sensitivity of Alaska's ecosystems to environmental change and anthropogenic disturbances using expert knowledge, remote sensing data, and spatiotemporal analyses and modeling. Time-series analysis of moderate-and high-resolution imagery was used to characterize land- and water-surface dynamics across Alaska. Some 430,000 interpretations of ecological and geomorphological change were made using historical air photos and satellite imagery, and corroborate land-surface greening, browning, and wetness/moisture trend parameters derived from peak-growing season Landsat imagery acquired from 1984 to 2015. The time series of change metrics, together with climatic data and maps of landscape characteristics, were incorporated into a modeling framework for mapping and understanding of drivers of change throughout Alaska. According to our analysis, approximately 13% (~174,000 ± 8700 km 2 ) of Alaska has experienced directional change in the last 32 years (±95% confidence intervals). At the ecoregions level, substantial increases in remotely sensed vegetation productivity were most pronounced in western and northern foothills of Alaska, which is explained by vegetation growth associated with increasing air temperatures. Significant browning trends were largely the result of recent wildfires in interior Alaska, but browning trends are also driven by increases in evaporative demand and surface-water gains that have predominately occurred over warming permafrost landscapes. Increased rates of photosynthetic activity are associated with stabilization and recovery processes following wildfire, timber harvesting, insect damage, thermokarst, glacial retreat, and lake infilling and drainage events. Our results fill a critical gap in the understanding of historical and potential future trajectories of change in northern high-latitude regions., (© 2018 John Wiley & Sons Ltd.)

Background: Penicillin skin testing (PST) is a novel way to reduce the use of broad-spectrum agents in penicillin-allergic patients. This study evaluated the outcomes of patients with antimicrobials prescribed with and without PST in a community health system., Methods: We performed a quasi-experimental study that compared an intervention group of 100 patients who completed PST over an open enrollment period beginning January 2016 with a matched control group of 100 patients who were penicillin allergic. Patients in the control group were matched to infection diagnosis codes of members of the PST group and randomly selected and matched on a 1:1 basis. The primary outcome was noncarbapenem beta-lactam days of therapy (DOT). The secondary outcome assessed the average cost of antimicrobial therapy for the intervention group before and after PST., Results: Seventy of the 98 patients (71%) who tested negative had changes directly made to their antimicrobial regimens. Beta-lactam DOT for the PST group were 666/1094 (60.88%, with 34.82% being a penicillin specifically). Beta-lactam DOT for the control group consisted of 386/984 (39.64%, with 6.4% being a penicillin specifically). The chi-square test of homogeneity for beta-lactam DOT between the 2 groups was significant ( P < .00001). Changes to the antimicrobial regimen after PST saved the average patient $353.03 compared with no change in the pre-PST regimen ( P = .045)., Conclusions: PST led to immediate antimicrobial de-escalation in the majority of patients who tested negative. This led to a significant increase in beta-lactam usage, specifically penicillins. These benefits were also associated with significant cost savings to patients.

Purpose: The purpose of this article is to offer practical guidance for pharmacists to successfully implement penicillin allergy skin testing (PAST)., Summary: Less than 10% of patients labeled as having a penicillin allergy are confirmed as present upon skin testing. This labeling results in use of alternative antibiotics and thus unwanted adverse consequences including potentiated antimicrobial resistance, increased costs, and worse clinical outcomes. Stewardship guidelines recommend PAST to enhance use of first-line agents; however, this was a weak recommendation with low-quality evidence. Recent efforts and subsequent research since publication of guidelines have demonstrated beneficial effects from increasing use of PAST among stewardship programs to improve outcomes. A number of different models exist demonstrating successful implementation of PAST at various healthcare facilities. There are important logistical factors to consider during implementation of PAST such as target population, optimal preparation, leadership structure, resource availability, and state regulations. Pharmacists as leaders of antimicrobial stewardship teams and experts in drug allergies are a natural fit to help implement PAST in healthcare settings to improve overall outcomes. This article offers guidance to institutions considering implementation of PAST., Conclusion: PAST is rapidly becoming an effective, long-term antimicrobial stewardship tool to optimize antimicrobial prescribing in both the inpatient and outpatient settings. Pharmacists have demonstrated significant benefit as providers of PAST services in a variety of healthcare settings with a number of different healthcare professionals.

The original version of this Article contained an error in the author affiliations. Affiliation 5 incorrectly read 'Tyumen State Oil and Gas University, Tyumen, Tyument. Oblast, Russian Federation, 625000'.This has now been corrected in both the PDF and HTML versions of the Article.

Local observations indicate that climate change and shifting disturbance regimes are causing permafrost degradation. However, the occurrence and distribution of permafrost region disturbances (PRDs) remain poorly resolved across the Arctic and Subarctic. Here we quantify the abundance and distribution of three primary PRDs using time-series analysis of 30-m resolution Landsat imagery from 1999 to 2014. Our dataset spans four continental-scale transects in North America and Eurasia, covering ~10% of the permafrost region. Lake area loss (-1.45%) dominated the study domain with enhanced losses occurring at the boundary between discontinuous and continuous permafrost regions. Fires were the most extensive PRD across boreal regions (6.59%), but in tundra regions (0.63%) limited to Alaska. Retrogressive thaw slumps were abundant but highly localized (<10 -5 %). Our analysis synergizes the global-scale importance of PRDs. The findings highlight the need to include PRDs in next-generation land surface models to project the permafrost carbon feedback.

For over a century, biologists have proposed a role for phenotypic plasticity in evolution, providing an avenue for adaptation in addition to 'mutation-first' models of evolutionary change. According to the various versions of this idea, the ability of organisms to respond adaptively to their environment through phenotypic plasticity may lead to novel phenotypes that can be screened by natural selection. If these initially environmentally induced phenotypes increase fitness, then genetic accommodation can lead to allele frequency change, influencing the expression of those phenotypes. Despite the long history of 'plasticity-first' models, the importance of genetic accommodation in shaping evolutionary change has remained controversial - it is neither fully embraced nor completely discarded by most evolutionary biologists. We suggest that the lack of acceptance of genetic accommodation in some cases is related to a lack of information on its molecular mechanisms. However, recent reports of epigenetic transgenerational inheritance now provide a plausible mechanism through which genetic accommodation may act, and we review this research here. We also discuss current evidence supporting a role for genetic accommodation in the evolution of eusociality in social insects, which have long been models for studying the influence of the environment on phenotypic variation, and may be particularly good models for testing hypotheses related to genetic accommodation. Finally, we introduce 'eusocial engineering', a method by which novel social phenotypes are first induced by environmental modification and then studied mechanistically to understand how environmentally induced plasticity may lead to heritable changes in social behavior. We believe the time is right to incorporate genetic accommodation into models of the evolution of complex traits, armed with new molecular tools and a better understanding of non-genetic heritable elements., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

This report describes the treatment of a 35-year-old male who presented to the emergency department with an empyema, and who had a long hospital course complicated by a catheter-related bloodstream infection and a history of intravenous drug use. Blood culture results confirmed Enterococcus faecalis. He was not a candidate for outpatient intravenous therapy and needed 14days of treatment, but was able to be discharged with a 3-day supply of oral levofloxacin to complete treatment for his empyema and 1 dose of dalbavancin at an outpatient infusion center to treat his bacteremia. Due to the unique properties of dalbavancin, off-label use in specific populations may help facilitate transitions of care. This report outlines the successful use of dalbavancin and removal of the central catheter in the treatment of E. faecalis bacteremia., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Multidrug-resistant Pseudomonas aeruginosa infections remain common in hospitals worldwide. We investigated the outcomes associated with the use of ceftolozane-tazobactam for the treatment of these infections., Methods: Data were collected retrospectively from 20 hospitals across the United States about adults who received ceftolozane-tazobactam for the treatment of multidrug-resistant P aeruginosa infections of any source for at least 24 hours. The primary outcome was a composite of 30-day and inpatient mortality, and secondary outcomes were clinical success and microbiological cure. Multivariable regression analysis was conducted to determine factors associated with outcomes., Results: Two-hundred five patients were included in the study. Severe illness and high degrees of comorbidity were common, with median Acute Physiology and Chronic Health Evaluation (APACHE) II scores of 19 (interquartile range [IQR], 11-24) and median Charlson Comorbidity Indexes of 4 (IQR, 3-6). Delayed initiation of ceftolozane-tazobactam was common with therapy started a median of 9 days after culture collection. Fifty-nine percent of patients had pneumonia. On susceptibility testing, 125 of 139 (89.9%) isolates were susceptible to ceftolozane-tazobactam. Mortality occurred in 39 patients (19%); clinical success and microbiological cure were 151 (73.7%) and 145 (70.7%), respectively. On multivariable regression analysis, starting ceftolozane-tazobactam within 4 days of culture collection was associated with survival (adjusted odds ratio [OR], 5.55; 95% confidence interval [CI], 2.14-14.40), clinical success (adjusted OR, 2.93; 95% CI, 1.40-6.10), and microbiological cure (adjusted OR, 2.59; 95% CI, 1.24-5.38)., Conclusions: Ceftolozane-tazobactam appeared to be effective in the treatment of multidrug-resistant P aeruginosa infections, particularly when initiated early after the onset of infection.

Increasing air temperatures are changing the arctic tundra biome. Permafrost is thawing, snow duration is decreasing, shrub vegetation is proliferating, and boreal wildlife is encroaching. Here we present evidence of the recent range expansion of North American beaver (Castor canadensis) into the Arctic, and consider how this ecosystem engineer might reshape the landscape, biodiversity, and ecosystem processes. We developed a remote sensing approach that maps formation and disappearance of ponds associated with beaver activity. Since 1999, 56 new beaver pond complexes were identified, indicating that beavers are colonizing a predominantly tundra region (18,293 km 2 ) of northwest Alaska. It is unclear how improved tundra stream habitat, population rebound following overtrapping for furs, or other factors are contributing to beaver range expansion. We discuss rates and likely routes of tundra beaver colonization, as well as effects on permafrost, stream ice regimes, and freshwater and riparian habitat. Beaver ponds and associated hydrologic changes are thawing permafrost. Pond formation increases winter water temperatures in the pond and downstream, likely creating new and more varied aquatic habitat, but specific biological implications are unknown. Beavers create dynamic wetlands and are agents of disturbance that may enhance ecosystem responses to warming in the Arctic., (© 2018 John Wiley & Sons Ltd.)

This work illustrates predominant measureable nonlinearities in photomultiplier tubes (PMTs) and introduces a controllable one called "Superlinearity," signifying both a positive nonlinear response and the ability to extend linear operation by counteracting gain saturation mechanisms - charge depletion, space-charge field limitation, and secondary emission surface effects. Recognizing superlinearity and its effect on the temporal step response leads to a true definition of linearity, free of a small-signal linear assumption. Furthermore, given the prevalent use of glass microchannel-plate (MCP) PMTs in favor of a faster impulse response in spite of a small charge limit, we are motivated to examine their nonlinear amplitude response and deploy tailored gain bias string methods to fully harness the maximum linear gain as is usually done for transmissive metal mesh and reflective metal dynode PMTs. Our characterization methodology applies standard NIST-traceable calibrated laboratory equipment with absolute input-referenced techniques, examining step responses over many orders of magnitude in controlled illumination. By doing so, we quantitatively reveal the superlinearity strength independent of charge depletion, yielding true linear responsivity and effectively doubling the small-signal linear limit; this is very relevant to PMT modeling and charge deconvolution efforts. With further development, the tailoring strategies we introduce could be applied to MCP detectors, extracting all useful capillary charge with a significant improvement in large linear signal quality.

Stroke has long been a devastating complication of any cardiovascular procedure that unfavorably affects survival and quality of life. Over time, strategies have been developed to substantially reduce the incidence of stroke after traditional cardiovascular procedures such as coronary artery bypass grafting, isolated valve surgery, and carotid endarterectomy. Subsequently, with the advent of minimally invasive technologies including percutaneous coronary intervention, carotid artery stenting, and transcatheter valve therapies, operators were faced with a new host of procedural risk factors, and efforts again turned toward identifying novel ways to reduce the risk of stroke. Fortunately, by understanding the procedural factors unique to these new techniques and applying many of the lessons learned from prior experiences, we are seeing significant improvements in the safety of these new technologies. In this review, the authors: 1) carefully analyze data from different cardiac procedural experiences ranging from traditional open heart surgery to percutaneous coronary intervention and transcatheter valve therapies; 2) explore the unique risk factors for stroke in each of these areas; and 3) describe how these risks can be mitigated with improved patient selection, adjuvant pharmacotherapy, procedural improvements, and novel technological advancements., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

DEPDC5 is a newly identified epilepsy-related gene implicated in focal epilepsy, brain malformations, and Sudden Unexplained Death in Epilepsy (SUDEP). In vitro, DEPDC5 negatively regulates amino acid sensing by the mTOR complex 1 (mTORC1) pathway, but the role of DEPDC5 in neurodevelopment and epilepsy has not been described. No animal model of DEPDC5-related epilepsy has recapitulated the neurological phenotypes seen in patients, and germline knockout rodent models are embryonic lethal. Here, we establish a neuron-specific Depdc5 conditional knockout mouse by cre-recombination under the Synapsin1 promotor. Depdc5 flox/flox -Syn1 Cre (Depdc5cc+) mice survive to adulthood with a progressive neurologic phenotype that includes motor abnormalities (i.e., hind limb clasping) and reduced survival compared to littermate control mice. Depdc5cc+ mice have larger brains with increased cortical neuron size and dysplastic neurons throughout the cortex, comparable to the abnormal neurons seen in human focal cortical dysplasia specimens. Depdc5 results in constitutive mTORC1 hyperactivation exclusively in neurons as measured by the increased phosphorylation of the downstream ribosomal protein S6. Despite a lack of increased mTORC1 signaling within astrocytes, Depdc5cc+ brains show reactive astrogliosis. We observed two Depdc5cc+ mice to have spontaneous seizures, including a terminal seizure. We demonstrate that as a group Depdc5cc+ mice have lowered seizure thresholds, as evidenced by decreased latency to seizures after chemoconvulsant injection and increased mortality from pentylenetetrazole-induced seizures. In summary, our neuron-specific Depdc5 knockout mouse model recapitulates clinical, pathological, and biochemical features of human DEPDC5-related epilepsy and brain malformations. We thereby present an important model in which to study targeted therapeutic strategies for DEPDC5-related conditions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Advancements in rapid diagnostics have helped to identify nutritionally variant streptococci (NVS) as an increasing cause of infective endocarditis (IE). This case report highlights the challenges in susceptibility testing and the importance of appropriate empiric treatment for Granulicatella adiacens, and provides considerations for future practice guideline recommendations. Guidelines for treatment of IE caused by NVS are currently limited to patients with native valve disease. We present a patient with presumed prosthetic valve endocarditis caused by G. adiacens, with clinically relevant resistance to recommended first-line agents (penicillin and ceftriaxone), who was successfully treated with 8 weeks of intravenous (IV) vancomycin. Vancomycin is currently recommended as an alternate therapy for patients intolerant of penicillins, but we believe vancomycin should be considered a first-line empiric treatment option for IE when the identified organism is G. adiacens and susceptibility testing is not readily available., (Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Pure methane (CH 4 /CD 4 ) ices were exposed to three ionizing radiation sources at 5.5 K under ultrahigh vacuum conditions to compare the complex hydrocarbon spectrum produced across several interstellar environments. These irradiation sources consisted of energetic electrons to simulate secondary electrons formed in the track of galactic cosmic rays (GCRs), Lyman α (10.2 eV; 121.6 nm) photons simulated the internal VUV field in a dense cloud, and broadband (112.7-169.8 nm; 11.0-7.3 eV) photons which mimic the interstellar ultra-violet field. The in situ chemical evolution of the ices was monitored via Fourier transform infrared spectroscopy (FTIR) and during heating via mass spectrometry utilizing a quadrupole mass spectrometer with an electron impact ionization source (EI-QMS) and a reflectron time-of-flight mass spectrometer with a photoionization source (PI-ReTOF-MS). The FTIR analysis detected six small hydrocarbon products from the three different irradiation sources: propane [C 3 H 8 (C 3 D 8 )], ethane [C 2 H 6 (C 2 D 6 )], the ethyl radical [C 2 H 5 (C 2 D 5 )], ethylene [C 2 H 4 (C 2 D 4 )], acetylene [C 2 H 2 (C 2 D 2 )], and the methyl radical [CH 3 (CD 3 )]. The sensitive PI-ReTOF-MS analysis identified a complex array of products with different products being detected between experiments with general formulae: C n H 2n+2 (n = 4-8), C n H 2n (n = 3-9), C n H 2n-2 (n = 3-9), C n H 2n-4 (n = 4-9), and C n H 2n-6 (n = 6-7) from electron irradiation and C n H 2n+2 (n = 4-8), C n H 2n (n = 3-10), C n H 2n-2 (n = 3-11), C n H 2n-4 (n = 4-11), C n H 2n-6 (n = 5-11), and C n H 2n-8 (n = 6-11) from broadband photolysis and Lyman α photolysis. These experiments show that even the simplest hydrocarbon can produce important complex hydrocarbons such as C 3 H 4 and C 4 H 6 isomers. Distinct isomers from these groups have been shown to be important reactants in the synthesis of polycyclic aromatic hydrocarbons like indene (C 9 H 8 ) and naphthalene (C 10 H 8 ) under interstellar conditions.

Arctic river deltas are highly dynamic environments in the northern circumpolar permafrost region that are affected by fluvial, coastal, and permafrost-thaw processes. They are characterized by thick sediment deposits containing large but poorly constrained amounts of frozen organic carbon and nitrogen. This study presents new data on soil organic carbon and nitrogen storage as well as accumulation rates from the Ikpikpuk and Fish Creek river deltas, two small, permafrost-dominated Arctic river deltas on the Arctic Coastal Plain of northern Alaska. A soil organic carbon storage of 42.4 ± 1.6 and 37.9 ± 3.5 kg C m - 2 and soil nitrogen storage of 2.1 ± 0.1 and 2.0 ± 0.2 kg N m - 2 was found for the first 2 m of soil for the Ikpikpuk and Fish Creek river delta, respectively. While the upper meter of soil contains 3.57 Tg C, substantial amounts of carbon (3.09 Tg C or 46%) are also stored within the second meter of soil (100-200 cm) in the two deltas. An increasing and inhomogeneous distribution of C with depth is indicative of the dominance of deltaic depositional rather than soil forming processes for soil organic carbon storage. Largely, mid- to late Holocene radiocarbon dates in our cores suggest different carbon accumulation rates for the two deltas for the last 2000 years. Rates up to 28 g C m - 2 year - 1 for the Ikpikpuk river delta are about twice as high as for the Fish Creek river delta. With this study, we highlight the importance of including these highly dynamic permafrost environments in future permafrost carbon estimations., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s) 2018, corrected publication August 2018.)

Lakes are dominant and diverse landscape features in the Arctic, but conventional land cover classification schemes typically map them as a single uniform class. Here, we present a detailed lake-centric geospatial database for an Arctic watershed in northern Alaska. We developed a GIS dataset consisting of 4362 lakes that provides information on lake morphometry, hydrologic connectivity, surface area dynamics, surrounding terrestrial ecotypes, and other important conditions describing Arctic lakes. Analyzing the geospatial database relative to fish and bird survey data shows relations to lake depth and hydrologic connectivity, which are being used to guide research and aid in the management of aquatic resources in the National Petroleum Reserve in Alaska. Further development of similar geospatial databases is needed to better understand and plan for the impacts of ongoing climate and land-use changes occurring across lake-rich landscapes in the Arctic.

Background: The impact of coronary artery disease (CAD) on outcomes after transcatheter aortic valve replacement (TAVR) is understudied. Literature on the prognostic role of CAD in the survival of patients undergoing TAVR shows conflicting results. This meta-analysis aims to investigate how CAD impacts patient survival following TAVR., Methods and Results: We completed a comprehensive literature search of Embase, MEDLINE, and the Cochrane Library, and included studies reporting outcome of TAVR based on CAD status of patients for the analysis. From the initial 1631 citations, 15 studies reporting on 8013 patients were analyzed using a random-effects model. Of the 8013 patients undergoing TAVR, with a median age of 81.3 years (79-85.1 years), 46.6% (40-55.7) were men and 3899 (48.7%) had CAD (ranging from 30.8% to 78.2% in various studies). Overall, 3121 SAPIEN/SAPIEN XT/SAPIEN 3 (39.6%) and 4763 CoreValve (60.4%) prostheses were implanted, with transfemoral access being the most frequently used approach for the implantation (76.1%). Our analysis showed no significant difference between patients with and without CAD for all-cause mortality at 30 days post TAVR, with a cumulative odds ratio of 1.07 (95% confidence interval, 0.82-1.40; P= 0.62). However, there was a significant increase in all-cause mortality at 1 year in the CAD group compared with patients without CAD, with a cumulative odds ratio of 1.21 (95% confidence interval, 1.07-1.36; P =0.002)., Conclusions: Even though coexisting CAD does not impact 30-day mortality, it does have an impact on 1-year mortality in patients undergoing TAVR. Our results highlight a need to revisit the revascularization strategies for concomitant CAD in patients with TAVR., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Transcatheter aortic valve implantation (TAVI) has become a widely accepted strategy for the treatment of aortic stenosis in patients at intermediate, high, or prohibitive surgical risk. After >1 decade of innovation and clinical trial experience, the available technology for TAVI has grown enormously, and now includes a myriad of vascular access approaches and innovative valve designs. As a result, the range of patients who can benefit from these advances continues to grow rapidly. Furthermore, given the improved safety profile and clinical success of current-generation devices in randomized trials, the use of TAVI among even low-risk populations is justified in current trials. With the rapid dissemination and expansion of this technology, operators need to have a comprehensive understanding of how to select the appropriate procedural approach for each individual patient. In this Review, we detail the current evidence for TAVI among different patient populations, discuss the different vascular access approaches currently in use, and explore differences in design features among currently available and investigational valve systems. Furthermore, we provide an overview of important considerations for special patient populations, such as those with existing mitral prostheses, bicuspid aortic stenosis, isolated aortic regurgitation, or severe left ventricular outflow tract calcification.

The prevalence of bovine trichomonosis (BT) in TN bulls was estimated through both active screening of bulls and review of previous laboratory records. During the active bull screening, preputial smegma specimens were collected from 458 TN beef bulls at 2 cattle slaughterhouses and 2 stockyards, which serve most beef bulls in TN, between March 2014 and June 2015. Each specimen was cultured for Tritrichomonas foetus (T. foetus) as well as evaluated microscopically every other day for seven days for any protozoa resembling T. foetus. An aliquot of the culture media from each specimen was used for DNA extraction and subsequent qPCR testing. Two specimens were considered suspect on microscopic evaluation, but all specimens were negative for T. foetus on qPCR. This suggests that the 2 specimens were most likely contaminated by fecal trichomonads. Retrospectively, 1979 T. foetus test records from 2 major TN diagnostic laboratories were reviewed between October 2013 and September 2016. True prevalence of BT in TN beef bulls was estimated at <0.01% from the laboratory records, although the county prevalence differed in 2 TN counties (Marshal: 0.09% and Bedford: 0.5%). Overall, the prevalence of BT in TN is low, and the current screening efforts to help control BT disease in TN are acceptable. Future efforts should focus on educating cattle stakeholders on the importance of optimal specimen collection and handling as well as routine testing for BT before cattle movement. In addition, cattle producers should be reminded of leading risk factors associated with BT in cattle., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Upwelling is the process by which deep, cold, relatively high-CO2, nutrient-rich seawater rises to the sunlit surface of the ocean. This seasonal process has fueled geoengineering initiatives to fertilize the surface ocean with deep seawater to enhance productivity and thus promote the drawdown of CO2. Coccolithophores, which inhabit many upwelling regions naturally 'fertilized' by deep seawater, have been investigated in the laboratory in the context of ocean acidification to determine the extent to which nutrients and CO2 impact their physiology, but few data exist in the field except from mesocosms. Here, we used the Porcupine Abyssal Plain (north Atlantic Ocean) Observatory to retrieve seawater from depths with elevated CO2 and nutrients, mimicking geoengineering approaches. We tested the effects of abrupt natural deep seawater fertilization on the physiology and biogeochemistry of two strains of Emiliania huxleyi of known physiology. None of the strains tested underwent cell divisions when incubated in waters obtained from <1,000 m (pH = 7.99-8.08; CO2 = 373-485 p.p.m; 1.5-12 μM nitrate). However, growth was promoted in both strains when cells were incubated in seawater from ~1,000 m (pH = 7.9; CO2 ~560 p.p.m.; 14-17 μM nitrate) and ~4,800 m (pH = 7.9; CO2 ~600 p.p.m.; 21 μM nitrate). Emiliania huxleyi strain CCMP 88E showed no differences in growth rate or in cellular content or production rates of particulate organic (POC) and inorganic (PIC) carbon and cellular particulate organic nitrogen (PON) between treatments using water from 1,000 m and 4,800 m. However, despite the N:P ratio of seawater being comparable in water from ~1,000 and ~4,800 m, the PON production rates were three times lower in one incubation using water from ~1,000 m compared to values observed in water from ~4,800 m. Thus, the POC:PON ratios were threefold higher in cells that were incubated in ~1,000 m seawater. The heavily calcified strain NZEH exhibited lower growth rates and PIC production rates when incubated in water from ~4,800 m compared to ~1,000 m, while cellular PIC, POC and PON were higher in water from 4,800 m. Calcite Sr/Ca ratios increased with depth despite constant seawater Sr/Ca, indicating that upwelling changes coccolith geochemistry. Our study provides the first experimental and field trial of a geoengineering approach to test how deep seawater impacts coccolithophore physiological and biogeochemical properties. Given that coccolithophore growth was only stimulated using waters obtained from >1,000 m, artificial upwelling using shallower waters may not be a suitable approach for promoting carbon sequestration for some locations and assemblages, and should therefore be investigated on a site-by-site basis.

Background: Reversibility of left ventricular (LV) dysfunction in high-risk aortic stenosis patient and its impact on survival after transcatheter aortic valve replacement (TAVR) are unclear. We aimed to evaluate longitudinal changes of LV structure and function after TAVR and their impact on survival., Methods and Results: We studied 209 patients with aortic stenosis who underwent TAVR from May 2006 to December 2012. Echocardiograms were used to calculate LV end-diastolic volume index (LVEDVi), LV ejection fraction, LV mass index (LVMi), and global longitudinal strain before, immediately (<10 days), late (1-3 months), and yearly after TAVR. During a median follow-up of 1345 days, 118 patients died, with 26 dying within 1 year. Global longitudinal strain, LVEDVi, LV ejection fraction, and LVMi improved during follow-up. In patients who died during the first year, death was preceded by LVEDVi and LVMi increase. Multivariable longitudinal data analysis showed that aortic regurgitation at baseline, aortic regurgitation at 30 days, and initial LVEDVi were independent predictors of subsequent LVEDVi. In a joint analysis of longitudinal and survival data, baseline Society of Thoracic Surgeons score was predictive of survival, with no additive effect of longitudinal changes in LVEDVi, LVMi, global longitudinal strain, or LV ejection fraction. Presence of aortic regurgitation at 1 month after TAVR was the only predictor of 1-year survival., Conclusions: LV reverse remodeling was observed after TAVR, whereas lack of LVEDVi and LVMi improvement was observed in patients who died during the first year after TAVR. Post-TAVR, aortic regurgitation blocks reverse remodeling and is associated with poor 1-year survival after TAVR., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Introduction: Stroke is a devastating, potential complication of any cardiovascular procedure including transcatheter aortic valve implantation (TAVI). Even clinically silent lesions as detected by magnetic resonance imaging have been associated with poor long-term cognitive outcomes. As a result, extensive efforts have been focused on developing stroke preventative strategies including the development of novel embolic protection devices. These devices aim to reduce this risk by capturing or deflecting emboli away from the cerebral circulation. Areas covered: This review provides an insight into the incidence and mechanisms of neurologic events during TAVI, explores the design features and initial human experience of each of the cerebral embolic protection devices that have been used during TAVI, and carefully explains the major clinical trials of each of these devices with a focus on safety, efficacy and other reported outcomes. Expert commentary: The potential benefit of neuroprotection cannot be ignored as TAVI widens its scope to include younger and lower-risk patients wherein preventing a procedure related cerebral injury would potentially prevent long-term morbidity and mortality.

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) governs antioxidant, innate immune and cytoprotective responses and its deregulation is prominent in chronic inflammatory conditions. To examine the hypothesis that Nrf2 might be implicated in systemic sclerosis (SSc), we investigated its expression, activity, and mechanism of action in SSc patient samples and mouse models of fibrosis and evaluated the effects of a novel pharmacologic Nrf2 agonist. We found that both expression and activity of Nrf2 were significantly reduced in SSc patient skin biopsies and showed negative correlation with inflammatory gene expression. In skin fibroblasts, Nrf2 mitigated fibrotic responses by blocking canonical transforming growth factor-β (TGF-β)-Smad signaling, whereas silencing Nrf2 resulted in constitutively elevated collagen synthesis, spontaneous myofibroblast differentiation, and enhanced TGF-ß responses. Bleomycin treatment of Nrf2-null mice resulted in exaggerated fibrosis. In wild-type mice, treatment with a novel pharmacologic Nrf2 agonist 2-trifluoromethyl-2'-methoxychalcone prevented dermal fibrosis induced by TGF-β. These findings are the first to identify Nrf2 as a cell-intrinsic antifibrotic factor with key roles in maintaining extracellular matrix homeostasis and a pathogenic role in SSc. Pharmacologic reactivation of Nrf2, therefore, represents a novel therapeutic strategy toward effective treatment of fibrosis in SSc., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Advances in sequencing technologies continue to provide unprecedented opportunities to characterize microbial communities. For example, the Pacific Biosciences Single Molecule Real-Time (SMRT) platform has emerged as a unique approach harnessing DNA polymerase activity to sequence template molecules, enabling long reads at low costs. With the aim to simultaneously classify and enumerate in situ microbial populations, we developed a quantitative SMRT (qSMRT) approach that involves the addition of exogenous standards to quantify ribosomal amplicons derived from environmental samples. The V7-9 regions of 18S SSU rDNA were targeted and quantified from protistan community samples collected in the Ross Sea during the Austral summer of 2011. We used three standards of different length and optimized conditions to obtain accurate quantitative retrieval across the range of expected amplicon sizes, a necessary criterion for analyzing taxonomically diverse 18S rDNA molecules from natural environments. The ability to concurrently identify and quantify microorganisms in their natural environment makes qSMRT a powerful, rapid and cost-effective approach for defining ecosystem diversity and function., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Complex surgery for appearance change is controversial. Correction of orbital hypertelorism risks diplopia and loss of stereopsis for aesthetic gain. The risk-to-benefit ratio remains ill-defined. The aim of this study was to define specific ocular morbidity following orbital translocation., Methods: The authors compared stable preoperative and postoperative orthoptic indices (i.e., angle of strabismus, ocular motility, and acuity) for 23 consecutive patients who underwent orbital translocation between 2000 and 2015 and noted the requirement for corrective surgery., Results: Eighteen patients underwent 33 box osteotomies (15 bilateral and three unilateral). Five patients underwent facial bipartition. Diagnosis was craniofrontonasal dysplasia in 11, frontonasal dysplasia in six, facial cleft in four, and Saethre-Chotzen syndrome in two cases. Median grade of orbital hypertelorism was III. Median age at surgery was 13 years (range, 5 to 17 years). Nontransient change (favorable or unfavorable) in angle of strabismus was noted in 14 patients. Ocular motility was altered in 12. Six patients had stereopsis preoperatively that was disrupted in two cases because of changes in ocular alignment and/or motility. There was one perioperative ophthalmic emergency (superior orbital fissure syndrome) and three acute reexplorations for external ocular muscle entrapment. Corrective surgery for strabismus was performed for four patients. Three required secondary canthopexy and three required surgery for blepharoptosis., Conclusions: Orbital translocation is associated with ocular risks including changes to angle of strabismus, ocular motility, and (when present) loss of stereopsis. Secondary surgery to correct strabismus or eyelid malposition is common. Orbital translocation is an operative process, not a single procedure., Clinical Question/level of Evidence: Therapeutic, IV.

Importance: Childhood arterial ischemic stroke (CAIS) affects approximately 1.6 per 100 000 children per year, while stroke recurs in up to 20% of patients at 5 years. Factors determining the risk of recurrence are incompletely understood., Objective: To investigate the incidence of the recurrence of CAIS in the posterior and anterior circulations to determine if the risk differs between the 2 locations., Design, Setting, and Participants: A retrospective analysis of CAIS was conducted among children enrolled in a single-center prospective consecutive cohort at The Children's Hospital of Philadelphia between January 1, 2006, and January 1, 2015. Children with confirmed CAIS occurring between 29 days and 17.99 years were evaluated for inclusion. Patients were excluded if infarcts were located in both the anterior and posterior distributions or if CAIS occurred as a complication of intracranial surgery or brain tumor., Main Outcomes and Measures: Stroke recurrence., Results: The study population included 107 patients (75 boys [70.1%] and 32 girls [29.9%]; median age at AIS, 7.7 years [interquartile range, 3.1-13.6 years]). Sixty-one children had anterior circulation CAIS (ACAIS) and 46 had posterior circulation CAIS (PCAIS). Median follow-up was 20.9 months (interquartile range, 8.7-40.4 months). For ACAIS, recurrence-free survival was 100% at 1 month and 96% (95% CI, 85%-99%) at 1 and 3 years. For PCAIS, recurrence-free survival was 88% (95% CI, 75%-95%) at 1 month and 81% (95% CI, 66%-90%) at 1 and 3 years. The hazard ratio for recurrence after PCAIS compared with ACAIS was 6.4 (95% CI, 1.4-29.8; P = .02) in univariable analysis and 5.3 (95% CI, 1.1-26.4; P = .04) after adjusting for sex and cervical dissection., Conclusions and Relevance: We identified a subgroup of patients that comprise more than 80% of recurrences of CAIS. Three years after incident stroke, 19% of children with PCAIS had a recurrence compared with 4% of patients with ACAIS. Different mechanisms of stroke may account for this difference. Children with PCAIS may warrant increased monitoring. This study highlights the necessity for further research focused on recurrence prevention.

Purpose: An initiative to determine the effects of penicillin skin testing (PST) from an antimicrobial stewardship perspective is described., Summary: Penicillin allergy is one of the most frequently reported allergies; however, only about 10% of self-reports of penicillin allergy are accurate. Incorrect penicillin allergies are therefore a significant barrier to antimicrobial stewardship, with important clinical and economic implications, including increased antimicrobial resistance, an increased overall cost of care, increased length of stay, and, ultimately, increased mortality. As part of its antimicrobial stewardship program, a community health system launched a PST initiative in order to optimize therapy, reduce adverse events acquisition costs, and minimize development of antibiotic resistance. The PST program involves the use of a standardized protocol for the assessment of hypersensitivity to penicillin in patients with suspected penicillin allergy. Among 36 patients who completed the PST protocol during an eight-month period, all had a negative result; in 27 of those patients, a conversion of antimicrobial therapy to a penicillin or cephalosporin was implemented as a direct result of PST., Conclusion: In patients with a self-reported penicillin allergy, PST led to a reduction in the use of carbapenems, aztreonam, vancomycin, and other broad-spectrum agents within a health system. A decrease in drug costs was documented in a sample of patients switched to a penicillin or a cephalosporin after PST., (Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

This study tests a social identity based mechanism for the effectiveness of plain tobacco packaging legislation, introduced in Australia in December 2012, to reduce cigarette smoking. 178 Australian smokers rated their sense of identification with fellow smokers of their brand, positive brand stereotypes, quitting behaviours and intentions, and smoking intensity, both before and seven months after the policy change. Mediation analyses showed that smokers, especially those who initially identified strongly with their brand, experienced a significant decrease in their brand identity following the introduction of plain packaging and this was associated with lower smoking behaviours and increased intentions to quit. The findings provide the first quantitative evidence that brand identities may help maintain smoking behaviour, and suggest the role of social-psychological processes in the effectiveness of public health policy.

Developmental plasticity may accelerate the evolution of phenotypic novelty through genetic accommodation, but studies of genetic accommodation often lack knowledge of the ancestral state to place selected traits in an evolutionary context. A promising approach for assessing genetic accommodation involves using a comparative framework to ask whether ancestral plasticity is related to the evolution of a particular trait. Bees are an excellent group for such comparisons because caste-based societies (eusociality) have evolved multiple times independently and extant species exhibit different modes of eusociality. We measured brain and abdominal gene expression in a facultatively eusocial bee, Megalopta genalis, and assessed whether plasticity in this species is functionally linked to eusocial traits in other bee lineages. Caste-biased abdominal genes in M. genalis overlapped significantly with caste-biased genes in obligately eusocial bees. Moreover, caste-biased genes in M. genalis overlapped significantly with genes shown to be rapidly evolving in multiple studies of 10 bee species, particularly for genes in the glycolysis pathway and other genes involved in metabolism. These results provide support for the idea that eusociality can evolve via genetic accommodation, with plasticity in facultatively eusocial species like M. genalis providing a substrate for selection during the evolution of caste in obligately eusocial lineages., (© 2017 The Author(s).)

Physical and mental health is known to have wide influence over most aspects of social life-be it schooling and employment or marriage and broader social engagement-but has received limited attention in explaining different forms of political participation. We analyze a unique dataset with a rich array of objective measures of cognitive and physical well-being and two objective measures of political participation, voting and contributing money to campaigns and parties. For voting, each aspect of health has a powerful effect on par with traditional predictors of participation such as education. In contrast, health has little to no effect on making campaign contributions. We recommend additional attention to the multifaceted affects of health on different forms of political participation.

Objective: Moderate to severe aortic regurgitation after transcatheter aortic valve replacement is associated with worse outcomes. The impact of mild aortic regurgitation has been less clear, possibly because of the broad categories that have been used in clinical trials, but holds increasing importance in the study of next-generation devices in low- and intermediate-risk cohorts. A more granular scheme, which is common in clinical practice and proposed for future trials, may add prognostic value., Methods: We evaluated all patients undergoing transfemoral transcatheter aortic valve replacement at the Cleveland Clinic from 2006 to 2012. The degree of aortic regurgitation after transcatheter aortic valve replacement was reported from the echocardiography database based on a clinical, transthoracic echocardiogram performed within 30 days of the procedure. Aortic regurgitation was finely discriminated on the basis of a multiwindow, multiparametric, integrative approach using our usual clinical scale: none, trivial to 1+, 1+, 1 to 2+, 2+, 2 to 3+, 3+, 3 to 4+, or 4+., Results: There were 237 patients included in the analysis. By controlling for age, gender, Society of Thoracic Surgeons score, baseline ejection fraction, and aortic regurgitation before transcatheter aortic valve replacement, there was a significant increase in mortality for each half grade of aortic regurgitation compared with the complete absence of aortic regurgitation after transcatheter aortic valve replacement. The unit hazard ratio for each 1+ increase in aortic regurgitation after transcatheter aortic valve replacement was 2.26 (95% confidence interval, 1.48-3.43; P < .001) considering aortic regurgitation as a continuous variable. Other clinical variables did not significantly affect mortality., Conclusions: Even mild aortic regurgitation after transcatheter aortic valve replacement is associated with worse long-term mortality. There may be prognostic value in reporting milder categories of aortic regurgitation with more granular gradations., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Honey bee colonies function as a superorganism, where facultatively sterile female workers perform various tasks that support the hive. Nurse workers undergo numerous anatomical and physiological changes in preparation for brood rearing, including the growth of hypopharyngeal glands (HGs). These glands produce the major protein fraction of a protein- and lipid-rich jelly used to sustain developing larvae. Pollen intake is positively correlated with HG growth, but growth in the first three days is similar regardless of diet, suggesting that initial growth is a pre-determined process while later HG development depends on nutrient availability during a critical window in early adulthood (>3 d). It is unclear whether the resultant size differences in nurse HG are simply due to growth arrest or active degradation of the tissue. To determine what processes cause such differences in HG size, we catalogued the differential expression of both gene transcripts and proteins in the HGs of 8 d old bees that were fed diets containing pollen or no pollen. 3438 genes and 367 proteins were differentially regulated due to nutrition. Of the genes and proteins differentially expressed, undernourished bees exhibited more gene and protein up-regulation compared to well-nourished bees, with the affected processes including salivary gland apoptosis, oogenesis, and hormone signaling. Protein secretion was virtually the only process up-regulated in well-nourished bees. Further assays demonstrated that inhibition of ultraspiracle, one component of the ecdysteroid receptor, in the fat body caused larger HGs. Undernourished bees also had higher acid phosphatase activity, a physiological marker of cell death, compared to well-nourished bees. These results support a connection between poor nutrition, hormonal signaling, and HG degradation., (Published by Elsevier Ltd.)

With the extirpation of apex predators from many North American systems, coyotes Canis latrans have become the de facto top predator and are ubiquitous members of most ecosystems. Keystone predators aid in maintaining ecosystem function by regulating the mammal community through direct predation and instilling the landscape of fear, yet the value of coyotes regulating systems to this capacity is understudied and likely variable across environments. Since coyotes are common in the Midwestern United States, we utilized camera traps and occupancy analyses to assess their role in regulating the distribution of mammalian herbivores in a fragmented suburban ecosystem. Forest cover was a strong positive predictor of white-tailed deer Odocoileus virginianus detection, while coyote occurrence had a negative effect. Coyotes exerted a negative effect on squirrel ( Sciurus spp.) and eastern cottontail rabbit Sylvilagus floridanus occurrence, while urban cover was a positive predictor for the prey species' occurrence. These results suggest all 3 species behaviorally avoid coyotes whereby deer seek denser forest cover and squirrels and cottontails mitigate risk by increasing use of urban areas. Although previous studies reveal limited influence of coyote on the rest of the carnivore guild in suburban systems, we suggest coyotes play an important role in regulating the herbivorous mammals and hence may provide similar ecological benefits in urban/suburban forest fragments through trophic cascades. Furthermore, since hunting may not be allowed in urban and suburban habitats, coyotes might also serve as the primary regulator of nuisance species occurring at high abundance such as white-tailed deer and squirrels.

Urea is considered a fundamental building block in prebiotic chemistry. Its formation on early Earth has not yet been explained satisfactorily and exogenous delivery has been considered. We report on the synthesis along with the first online and in situ identification of urea after exposing inorganic ices to ionizing radiation.