Searching for Failed Supernovae With Astrometric Binaries

Stars in the mass range 8 Msun<M<30 Msun are thought to end their lives as luminous supernovae that leave behind a neutron star. However, if a substantial fraction of these stars instead ended as black-hole remnants, without producing a supernova (a `failed' supernova), how would one know? We show that, under plausible assumptions, the Hipparcos catalog should contain about 30 f_{fail} astrometric binaries with black-hole companions, where f_{fail} is the fraction of supernovae that fail. Since no black-hole astrometric binaries are found in Hipparcos, one might like to conclude that such failed supernovae are very rare. However, the most important assumption required for this argument, the initial companion mass function (ICMF) of G stars (the majority of Hipparcos stars) in the high-mass companion regime, is without any observational basis. We show how the ICMF of G stars can be measured using the Full-Sky Astrometric Explorer (FAME), thereby permitting an accurate measurement of the rate of supernovae that fail.Comment: Submitted to ApJ, 14 pages including 4 figure

Cost-minimisation analysis of a treat-and-extend regimen with anti-VEGFs in patients with neovascular age-related macular degeneration

PURPOSE: Although intraocular anti-vascular endothelial growth factors (anti-VEGFs) are effective as treatment of neovascular age-related macular degeneration (nAMD), the (economic) burden on the healthcare system is considerable. A treat-and-extend (T&E) regimen is associated with a lower number of injections without compromising the effectiveness and can therefore help optimise nAMD treatment. This study investigates the per-patient costs associated with nAMD treatment, when using aflibercept, bevacizumab, or ranibizumab with a T&E regimen. METHODS: In this cost-minimisation model, the per-patient costs in the Netherlands were modelled using a healthcare payers’ perspective over a 3-year time horizon with the assumption that efficacy of treatments is similar. Additionally, the break-even price of the different anti-VEGFs was calculated relative to the cheapest option and injection frequency. RESULTS: The injection frequency varied from 14.2 for aflibercept to 27.4 for bevacizumab in 3 years. Nonetheless, bevacizumab remains the cheapest treatment option (€14,215), followed by aflibercept (€18,202) and ranibizumab (€31,048). The medication covers the majority of the per-patient costs for aflibercept and ranibizumab, while administration covers the majority of the per-patient costs for bevacizumab. The break-even prices of aflibercept and ranibizumab are respectively €507 and €60.58 per injection. Brolucizumab was included in the scenario analysis and was more expensive than aflibercept (€20,446). Brolucizumab should reduce to 13.8 injections over 3 years to be as costly as aflibercept. CONCLUSION: Bevacizumab is the cheapest anti-VEGF treatment. The list prices of all anti-VEGFs should reduce to be as costly as bevacizumab. Aflibercept is the second-choice treatment and so far brolucizumab is not

Loss of Potential Aquatic-Terrestrial Subsidies Along the Missouri River Floodplain

The floodplains of large rivers have been heavily modified due to riparian development and channel modifications, both of which can eliminate shallow off-channel habitats. The importance of these habitats for aquatic organisms like fishes is well studied. However, loss of off-channel habitat also eliminates habitats for the production of emerging aquatic insects, which subsidize riparian consumers in terrestrial food webs. We used field collections of insect emergence, historical mapping, and statistical modeling to estimate the loss of insect emergence due to channel modifications along eight segments of the Missouri River (USA), encompassing 1566 river km, between 1890 and 2012. We estimate annual production of emerging aquatic insects declined by a median of 36,000 kgC (95% CrI: 3000 to 450,000) between 1890 and 2012 (a 34% loss), due to the loss of surface area in backwaters and related off-channel habitats. Under a conservative assumption that riparian birds obtain 24% of their annual energy budget from adult aquatic insects, this amount of insect loss would be enough to subsidize approximately 790,000 riparan woodland birds during the breeding and nesting period (May to August; 95% CrI: 57,000 to 10,000,000). Most of the loss is concentrated in the lower reaches of the Missouri River, which historically had a wide floodplain, a meandering channel, and a high density of off-channel habitats, but which were substantially reduced due to channelization and bank stabilization. Our results indicate that the loss of off-channel habitats in large river floodplains has the potential to substantially affect energy availability for riparian insectivores, further demonstrating the importance of maintaining and restoring these habitats for linked aquatic-terrestrial ecosystems

Multidimensional Atomic Force Microscopy: A Versatile Novel Technology for Nanopharmacology Research

Nanotechnology is giving us a glimpse into a nascent field of nanopharmacology that deals with pharmacological phenomena at molecular scale. This review presents our perspective on the use of scanning probe microscopy techniques with special emphasis to multidimensional atomic force microscopy (m-AFM) to explore this new field with a particular emphasis to define targets, design therapeutics, and track outcomes of molecular-scale pharmacological interactions. The approach will be to first discuss operating principles of m-AFM and provide representative examples of studies to understand human health and disease at the molecular level and then to address different strategies in defining target macromolecules, screening potential drug candidates, developing and characterizing of drug delivery systems, and monitoring target–drug interactions. Finally, we will discuss some future directions including AFM tip-based parallel sensors integrated with other high-throughput technologies which could be a powerful platform for drug discovery

Rapid, ultra low coverage copy number profiling of cell-free DNA as a precision oncology screening strategy.

Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling. We applied PRINCe to a retrospective cohort of 124 cfDNA samples from 100 patients with advanced cancers, including 76 men with metastatic castration-resistant prostate cancer (mCRPC), enabling cfDNA tumor content approximation and actionable focal CNA detection, while facilitating concordance analyses between cfDNA and tissue-based NGS profiles and assessment of cfDNA alteration associations with mCRPC treatment outcomes. Therapeutically relevant focal CNAs were present in 42 (34%) cfDNA samples, including 36 of 93 (39%) mCRPC patient samples harboring AR amplification. PRINCe identified pre-treatment cfDNA CNA profiles facilitating disease monitoring. Combining PRINCe with routine targeted NGS of cfDNA enabled mutation and CNA assessment with coverages tuned to cfDNA tumor content. In mCRPC, genome-wide PRINCe cfDNA and matched tissue CNA profiles showed high concordance (median Pearson correlation = 0.87), and PRINCe detectable AR amplifications predicted reduced time on therapy, independent of therapy type (Kaplan-Meier log-rank test, chi-square = 24.9, p &lt; 0.0001). Our screening approach enables robust, broadly applicable cfDNA-based precision oncology for patients with advanced cancer through scalable identification of therapeutically relevant CNAs and pre-/post-treatment genomic profiles, enabling cfDNA- or tissue-based precision oncology workflow optimization

Prioritization of fish communities with a view to conservation and restoration on a large scale European basin, the Loire (France)

The hierarchical organization of important sites for the conservation or the restoration of fish communities is a great challenge for managers, especially because of financial or time constraints. In this perspective, we developed a methodology, which is easy to implement in different locations. Based on the fish assemblage characteristics of the Loire basin (France), we created a synthetic conservation value index including the rarity, the conservation status and the species origin. The relationship between this new synthetic index and the Fish-Based Index allowed us to establish a classification protocol of the sites along the Loire including fish assemblages to be restored or conserved. Sites presenting disturbed fish assemblages, a low rarity index, few threatened species, and a high proportion of non-native species were considered as important for the restoration of fish biodiversity. These sites were found mainly in areas where the assemblages are typical of the bream zone, e.g. with a higher number of eurytopic and limnophilic species. On the contrary, important sites for conservation were defined as having an important conservation potential (high RI, a lot of threatened species, and few nonnatives fish species) and an undisturbed fish assemblage similar to the expected community if habitats are undisturbed. Important sites for conservation were found in the Loire basin’s medium reaches which host assemblages typical for the grayling and the barbell zones, e.g. with a higher number of rheophilic species. The synthetic conservation value index could be adapted and completed with other criteria according to management priorities and capacities

The Primordial Binary Population - I: A near-infrared adaptive optics search for close visual companions to A star members of Scorpius OB2

We present the results of a near-infrared adaptive optics survey with the aim to detect close companions to Hipparcos members in the three subgroups of the nearby OB association Sco OB2: Upper Scorpius (US), Upper Centaurus Lupus (UCL) and Lower Centaurus Crux (LCC). We have targeted 199 A-type and late B-type stars in the Ks band, and a subset also in the J and H band. We find 151 stellar components other than the target stars. A brightness criterion is used to separate these components into 77 background stars and 74 candidate physical companion stars. Out of these 74 candidate companions, 41 have not been reported before (14 in US; 13 in UCL; 14 in LCC). Companion star masses range from 0.1 to 3 Msun. The mass ratio distribution follows f(q) = q^-0.33, which excludes random pairing. No close (rho < 3.75'') companion stars or background stars are found in the magnitude range 12 < Ks < 14. The lack of stars with these properties cannot be explained by low-number statistics, and may imply a lower limit on the companion mass of ~ 0.1 Msun. Close stellar components with Ks > 14 are observed. If these components are very low-mass companion stars, a gap in the companion mass distribution might be present. The small number of close low-mass companion stars could support the embryo-ejection formation scenario for brown dwarfs. Our findings are compared with and complementary to visual, spectroscopic, and astrometric data on binarity in Sco OB2. We find an overall companion star fraction of 0.52 in this association. This paper is the first step toward our goal to derive the primordial binary population in Sco OB2.Comment: 27 pages, to accepted by A&

Combined effects of warming and drought on plant biomass depend on plant woodiness and community type: a meta-analysis.

Global warming and precipitation extremes (drought or increased precipitation) strongly affect plant primary production and thereby terrestrial ecosystem functioning. Recent syntheses show that combined effects of warming and precipitation extremes on plant biomass are generally additive, while individual experiments often show interactive effects, indicating that combined effects are more negative or positive than expected based on the effects of single factors. Here, we examined whether variation in biomass responses to single and combined effects of warming and precipitation extremes can be explained by plant growth form and community type. We performed a meta-analysis of 37 studies, which experimentally crossed warming and precipitation treatments, to test whether biomass responses to combined effects of warming and precipitation extremes depended on plant woodiness and community type (monocultures versus mixtures). Our results confirmed that the effects of warming and precipitation extremes were overall additive. However, combined effects of warming and drought on above- and belowground biomass were less negative in woody- than in herbaceous plant systems and more negative in plant mixtures than in monocultures. We further show that drought effects on plant biomass were more negative in greenhouse, than in field studies, suggesting that greenhouse experiments may overstate drought effects in the field. Our results highlight the importance of plant system characteristics to better understand plant responses to climate change

Crater formation by fast ions: comparison of experiment with Molecular Dynamics simulations

An incident fast ion in the electronic stopping regime produces a track of excitations which can lead to particle ejection and cratering. Molecular Dynamics simulations of the evolution of the deposited energy were used to study the resulting crater morphology as a function of the excitation density in a cylindrical track for large angle of incidence with respect to the surface normal. Surprisingly, the overall behavior is shown to be similar to that seen in the experimental data for crater formation in polymers. However, the simulations give greater insight into the cratering process. The threshold for crater formation occurs when the excitation density approaches the cohesive energy density, and a crater rim is formed at about six times that energy density. The crater length scales roughly as the square root of the electronic stopping power, and the crater width and depth seem to saturate for the largest energy densities considered here. The number of ejected particles, the sputtering yield, is shown to be much smaller than simple estimates based on crater size unless the full crater morphology is considered. Therefore, crater size can not easily be used to estimate the sputtering yield.Comment: LaTeX, 7 pages, 5 EPS figures. For related figures/movies, see: http://dirac.ms.virginia.edu/~emb3t/craters/craters.html New version uploaded 5/16/01, with minor text changes + new figure

Fish Species of Greatest Conservation Need in Wadeable Iowa Streams: Current Status and Effectiveness of Aquatic Gap Program Distribution Models

Effective conservation of fish species of greatest conservation need (SGCN) requires an understanding of species– habitat relationships and distributional trends. Thus, modeling the distribution of fish species across large spatial scales may be a valuable tool for conservation planning. Our goals were to evaluate the status of 10 fish SGCN in wadeable Iowa streams and to test the effectiveness of IowaAquatic Gap Analysis Project (IAGAP) species distribution models. We sampled fish assemblages from 86 wadeable stream segments in the Mississippi River drainage of Iowa during 2009 and 2010 to provide contemporary, independent fish species presence–absence data. The frequencies of occurrence in stream segments where species were historically documented varied from 0.0% for redfin shiner Lythrurus umbratilis to 100.0% for American brook lamprey Lampetra appendix, with a mean of 53.0%, suggesting that the status of Iowa fish SGCN is highly variable. Cohen’s kappa values and other model performance measures were calculated by comparing field-collected presence–absence data with IAGAP model–predicted presences and absences for 12 fish SGCN. Kappa values varied from 0.00 to 0.50, with a mean of 0.15. The models only predicted the occurrences of banded darter Etheostoma zonale, southern redbelly dace Phoxinus erythrogaster, and longnose dace Rhinichthys cataractae more accurately than would be expected by chance. Overall, the accuracy of the twelve models was low, with a mean correct classification rate of 58.3%. Poor model performance probably reflects the difficulties associated with modeling the distribution of rare species and the inability of the large-scale habitat variables used in IAGAP models to explain the variation in fish species occurrences. Our results highlight the importance of quantifying the confidence in species distribution model predictions with an independent data set and the need for long-term monitoring to better understand the distributional trends and habitat associations of fish SGCN