The Influence of Operational Resources and Activities on Indirect Personnel Costs: A Multilevel Modeling Approach

Indirect activities often represent an underemphasized, yet significant, contributing source of costs for organizations. In order to manage indirect costs, organizations must understand how these costs behave relative to changes in operational resources and activities. This is of particular interest to the Air Force and its sister services, because recent and projected reductions in defense spending are forcing reductions in their operational variables, and insufficient research exists to help them understand how this may influence indirect costs. Furthermore, although academic research on indirect costs has advanced the knowledge behind the modeling and behavior of indirect costs, significant gaps in the literature remain. Our research provides important and timely advances to the indirect cost literature. First, our research disaggregates the indirect cost pool and focuses on indirect personnel costs, which represent 33% of all Air Force indirect costs and are a leading source of indirect costs in many organizations. Second, we employ a multilevel modeling approach to capture the hierarchical nature of an enterprise, allowing us to assess the influence that each level of an organization has on indirect cost behavior and relationships. Third, we identify the operational variables that influence indirect personnel costs in the Air Force enterprise, providing Air Force decision-makers with evidence-based knowledge to inform decisions regarding budget reduction strategies

The Role of Forest Elephants in Shaping Tropical Forest-Savanna Coexistence

Forest edges that border savanna are dynamic features of tropical landscapes. Although the role of fire in determining edge dynamics has been relatively well explored, the role of mega-herbivores, specifically elephants, has not received as much attention. We investigated the role of forest elephants in shaping forest edges of the forest–savanna mosaic in Lopé National Park, Gabon. Using forty camera traps, we collected 1.2 million images between May 2016 and June 2017. These images were classified by over 10,000 volunteers through an online citizen science platform. These data were combined with a 33-year phenology dataset on elephant-favoured fruiting tree species, and field measurements of elephant browsing preferences and damage. Our results showed a strong relationship between forest elephant density at the forest edge and fruit availability. When fruit availability was high, elephant density at the edge reached values nearly double the highest densities ever reported in any other part of the landscape (7.5 elephants km−2 in this study vs the previous highest estimate of 4 elephants km−2). The highest elephant densities occurred at the end of the dry season, but even outside of this high density period elephant density at the forest edge (2.4 elephants km−2) was more than double what other studies estimate for forest interiors with low human hunting pressure (1 elephant km−2). We found forest elephants to be selective browsers, but their browsing was non-destructive (in contrast to savanna elephants) and had little effect on tree size demography. Elephant paths acted as firebreaks during savanna burning, making them inadvertent protectors of the fire-sensitive forest and contributing to the stabilising feedbacks that allow forest and savanna to coexist in tropical landscapes

Single and Multi-trait GWAS Identify Genetic Factors Associated with Production Traits in Common Bean Under Abiotic Stress Environments

The genetic improvement of economically important production traits of dry bean (Phaseolus vulgaris L.), for geographic regions where production is threatened by drought and high temperature stress, is challenging because of the complex genetic nature of these traits. Large scale SNP data sets for the two major gene pools of bean, Andean and Middle American, were developed by mapping multiple pools of genotype-by-sequencing reads and identifying over 200k SNPs for each gene pool against the most recent assembly of the P. vulgaris genome sequence. Moderately sized Bean Abiotic Stress Evaluation (BASE) panels, consisting of genotypes appropriate for production in Central America and Africa, were assembled. Phylogenetic analyses demonstrated the BASE populations represented broad genetic diversity for the appropriate races within the two gene pools. Joint mixed linear model genome-wide association studies with data from multiple locations discovered genetic factors associated with four production traits in both heat and drought stress environments using the BASE panels. Pleiotropic genetic factors were discovered using a multi-trait mixed model analysis. SNPs within or near candidate genes associated with hormone signaling, epigenetic regulation, and ROS detoxification under stress conditions were identified and can be used as genetic markers in dry bean breeding programs. Includes Corrigendu

Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance

BACKGROUND: Preventing the emergence of anti-malarial drug resistance is critical for the success of current malaria elimination efforts. Prevention strategies have focused predominantly on qualitative factors, such as choice of drugs, use of combinations and deployment of multiple first-line treatments. The importance of anti-malarial treatment dosing has been underappreciated. Treatment recommendations are often for the lowest doses that produce "satisfactory" results. METHODS: The probability of de-novo resistant malaria parasites surviving and transmitting depends on the relationship between their degree of resistance and the blood concentration profiles of the anti-malarial drug to which they are exposed. The conditions required for the in-vivo selection of de-novo emergent resistant malaria parasites were examined and relative probabilities assessed. RESULTS: Recrudescence is essential for the transmission of de-novo resistance. For rapidly eliminated anti-malarials high-grade resistance can arise from a single drug exposure, but low-grade resistance can arise only from repeated inadequate treatments. Resistance to artemisinins is, therefore, unlikely to emerge with single drug exposures. Hyperparasitaemic patients are an important source of de-novo anti-malarial drug resistance. Their parasite populations are larger, their control of the infection insufficient, and their rates of recrudescence following anti-malarial treatment are high. As use of substandard drugs, poor adherence, unusual pharmacokinetics, and inadequate immune responses are host characteristics, likely to pertain to each recurrence of infection, a small subgroup of patients provides the particular circumstances conducive to de-novo resistance selection and transmission. CONCLUSION: Current dosing recommendations provide a resistance selection opportunity in those patients with low drug levels and high parasite burdens (often children or pregnant women). Patients with hyperparasitaemia who receive outpatient treatments provide the greatest risk of selecting de-novo resistant parasites. This emphasizes the importance of ensuring that only quality-assured anti-malarial combinations are used, that treatment doses are optimized on the basis of pharmacodynamic and pharmacokinetic assessments in the target populations, and that patients with heavy parasite burdens are identified and receive sufficient treatment to prevent recrudescence

A distinct ecotonal tree community exists at central African forest-savanna transitions

1. Global change is expected to increase savanna woody encroachment as well as fire spreading into forest. Forest‐savanna ecotones are the frontier of these processes and can thus either mitigate or enhance the effects of global change. However, the ecology of the forest‐savanna ecotone is poorly understood. In this study, we determined whether a distinct ecotonal tree community existed between forest and savanna. We then evaluated whether the ecotonal tree community was more likely to facilitate fire spreading into the forest, woody encroachment of the savanna, or the stabilisation of both forest and savanna parts of the landscape. 2. We sampled twenty‐eight vegetation transects across forest‐savanna ecotones in a central African forest‐savanna mosaic. We collected data on the size and species of all established (basal diameter >3cm) trees in each transect. Split moving window dissimilarity analysis detected the location of borders delineating savanna, ecotone, and forest tree communities. We assessed whether the ecotonal tree community was likely to facilitate fire spreading into the forest by burning experimental fires and evaluating shade and grass biomass along the transects. To decide if the ecotone was likely to facilitate woody encroachment of the savanna we evaluated if ecotonal tree species were forest pioneers. 3. A compositionally distinct and spatially extensive ecotonal tree community existed between forest and savanna. The ecotonal tree community did not promote fire spreading into forest and instead acted as a fire buffer, shading out flammable grass biomass from the understorey and protecting the forest from 95% of savanna fires. The ecotone helped stabilise the forest‐savanna mosaic by allowing the fire‐dependant savanna to burn without exposing the fire‐sensitive forest to lethal temperatures. 4. The ecotonal tree community was comprised of many forest pioneer species that will promote woody encroachment in the savanna, especially if fire frequency is decreased. SYNTHESIS: A distinct fire‐buffering ecotonal tree community in this forest‐savanna mosaic landscape illustrated that savanna fires are unlikely to compromise forest integrity. Conversely, suppression of fire in this landscape will likely lead to loss of savanna as the ecotone becomes the frontier of woody encroachment. Regular burning is essential for the preservation of this forest‐savanna mosaic

Discovery of a Novel Compound with Anti-Venezuelan Equine Encephalitis Virus Activity That Targets the Nonstructural Protein 2

Abstract Alphaviruses present serious health threats as emerging and re-emerging viruses. Venezuelan equine encephalitis virus (VEEV), a New World alphavirus, can cause encephalitis in humans and horses, but there are no therapeutics for treatment. To date, compounds reported as anti-VEEV or anti-alphavirus inhibitors have shown moderate activity. To discover new classes of anti-VEEV inhibitors with novel viral targets, we used a high-throughput screen based on the measurement of cell protection from live VEEV TC-83-induced cytopathic effect to screen a 340,000 compound library. Of those, we identified five novel anti-VEEV compounds and chose a quinazolinone compound, CID15997213 (IC50 = 0.84 µM), for further characterization. The antiviral effect of CID15997213 was alphavirus-specific, inhibiting VEEV and Western equine encephalitis virus, but not Eastern equine encephalitis virus. In vitro assays confirmed inhibition of viral RNA, protein, and progeny synthesis. No antiviral activity was detected against a select group of RNA viruses. We found mutations conferring the resistance to the compound in the N-terminal domain of nsP2 and confirmed the target residues using a reverse genetic approach. Time of addition studies showed that the compound inhibits the middle stage of replication when viral genome replication is most active. In mice, the compound showed complete protection from lethal VEEV disease at 50 mg/kg/day. Collectively, these results reveal a potent anti-VEEV compound that uniquely targets the viral nsP2 N-terminal domain. While the function of nsP2 has yet to be characterized, our studies suggest that the protein might play a critical role in viral replication, and further, may represent an innovative opportunity to develop therapeutic interventions for alphavirus infection. Author Summary Alphaviruses occur worldwide, causing significant diseases such as encephalitis or arthritis in humans and animals. In addition, some alphaviruses, such as VEEV, pose a biothreat due to their high infectivity and lack of available treatments. To discover small molecule inhibitors with lead development potential, we used a cell-based assay to screen 348,140 compounds for inhibition of a VEEV-induced cytopathic effect. The screen revealed a scaffold with high inhibitory VEEV cellular potency and low cytotoxicity liability. While most previously reported anti-alphavirus compounds inhibit host proteins, evidence supported that this scaffold targeted the VEEV nsP2 protein, and that inhibition was associated with viral replication. Interestingly, compound resistance studies with VEEV mapped activity to the N-terminal domain of nsP2, to which no known function has been attributed. Ultimately, this discovery has delivered a small molecule-derived class of potent VEEV inhibitors whose activity is coupled to the nsP2 viral protein, a novel target with a previously unestablished biological role that is now implicated in viral replication.This research was supported by the following funding sources: NIH R03MH087448-01A1, University of Louisville Internal Research Initiate grant to DHC, USAMRAA W81XWH-10-2-0064 and W81XWH-08-2-0024 to CBJ. Screening was provided by the Southern Research Specialized Screening Center (U54HG005034-0) and chemistry through the University of Kansas Specialized Chemistry Center (U54HG005031). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Measurement of the Inclusive Semi-electronic D0D^0 Branching Fraction

Using the angular correlation between the $\pi^+$ emitted in a $D^{*+} \rightarrow D^0 \pi^+$ decay and the $e^+$ emitted in the subsequent $D^0 \rightarrow Xe^+\nu$ decay, we have measured the branching fraction for the inclusive semi-electronic decay of the $D^0$ meson to be: {\cal B}(D^0 \rightarrow X e^+ \nu) = [6.64 \pm 0.18 (stat.) \pm 0.29 (syst.)] \%. The result is based on 1.7 fb$^{-1}$ of $e^+e^-$ collisions recorded by the CLEO II detector located at the Cornell Electron Storage Ring (CESR). Combining the analysis presented in this paper with previous CLEO results we find, \frac{{\cal B} (D^0 \rightarrow X e^+ \nu)} {{\cal B} (D^0 \rightarrow K^- \pi^+)} = 1.684 \pm 0.056 (stat.) \pm 0.093(syst.) and \frac{{\cal B}(D\rightarrow K^-e^+\nu)} {{\cal B}(D\rightarrow Xe^+\nu)} = 0.581 \pm 0.023 (stat.) \pm 0.028(syst.). The difference between the inclusive rate and the sum of the measured exclusive branching fractions (measured at CLEO and other experiments) is $(3.3 \pm 7.2) \%$ of the inclusive rate.Comment: Latex file, 33pages, 4 figures Submitted to PR

Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19

BACKGROUND Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (Covid-19) on the basis of in vitro activity and data from uncontrolled studies and small, randomized trials. METHODS In this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality. RESULTS The enrollment of patients in the hydroxychloroquine group was closed on June 5, 2020, after an interim analysis determined that there was a lack of efficacy. Death within 28 days occurred in 421 patients (27.0%) in the hydroxychloroquine group and in 790 (25.0%) in the usual-care group (rate ratio, 1.09; 95% confidence interval [CI], 0.97 to 1.23; P=0.15). Consistent results were seen in all prespecified subgroups of patients. The results suggest that patients in the hydroxychloroquine group were less likely to be discharged from the hospital alive within 28 days than those in the usual-care group (59.6% vs. 62.9%; rate ratio, 0.90; 95% CI, 0.83 to 0.98). Among the patients who were not undergoing mechanical ventilation at baseline, those in the hydroxychloroquine group had a higher frequency of invasive mechanical ventilation or death (30.7% vs. 26.9%; risk ratio, 1.14; 95% CI, 1.03 to 1.27). There was a small numerical excess of cardiac deaths (0.4 percentage points) but no difference in the incidence of new major cardiac arrhythmia among the patients who received hydroxychloroquine. CONCLUSIONS Among patients hospitalized with Covid-19, those who received hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care. (Funded by UK Research and Innovation and National Institute for Health Research and others; RECOVERY ISRCTN number, ISRCTN50189673; ClinicalTrials.gov number, NCT04381936.

Pantropical modelling of canopy functional traits using Sentinel-2 remote sensing data

Tropical forest ecosystems are undergoing rapid transformation as a result of changing environmental conditions and direct human impacts. However, we cannot adequately understand, monitor or simulate tropical ecosystem responses to environmental changes without capturing the high diversity of plant functional characteristics in the species-rich tropics. Failure to do so can oversimplify our understanding of ecosystems responses to environmental disturbances. Innovative methods and data products are needed to track changes in functional trait composition in tropical forest ecosystems through time and space. This study aimed to track key functional traits by coupling Sentinel-2 derived variables with a unique data set of precisely located in-situ measurements of canopy functional traits collected from 2434 individual trees across the tropics using a standardised methodology. The functional traits and vegetation censuses were collected from 47 field plots in the countries of Australia, Brazil, Peru, Gabon, Ghana, and Malaysia, which span the four tropical continents. The spatial positions of individual trees above 10 cm diameter at breast height (DBH) were mapped and their canopy size and shape recorded. Using geo-located tree canopy size and shape data, community-level trait values were estimated at the same spatial resolution as Sentinel-2 imagery (i.e. 10 m pixels). We then used the Geographic Random Forest (GRF) to model and predict functional traits across our plots. We demonstrate that key plant functional traits can be accurately predicted across the tropicsusing the high spatial and spectral resolution of Sentinel-2 imagery in conjunction with climatic and soil information. Image textural parameters were found to be key components of remote sensing information for predicting functional traits across tropical forests and woody savannas. Leaf thickness (R2 = 0.52) obtained the highest prediction accuracy among the morphological and structural traits and leaf carbon content (R2 = 0.70) and maximum rates of photosynthesis (R2 = 0.67) obtained the highest prediction accuracy for leaf chemistry and photosynthesis related traits, respectively. Overall, the highest prediction accuracy was obtained for leaf chemistry and photosynthetic traits in comparison to morphological and structural traits. Our approach offers new opportunities for mapping, monitoring and understanding biodiversity and ecosystem change in the most species-rich ecosystems on Earth