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Human respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are frequent drivers of morbidity and mortality in susceptible populations, most often infantile, older adults, and immunocompromised. The primary target of neutralizing antibodies is the fusion (F) glycoprotein on the surface of the RSV and hMPV virion. As a result of the structural conservation between RSV and hMPV F, three antigenic regions are known to induce cross-neutralizing responses: sites III, IV, and V. Leveraging LIBRA-seq, we identify five RSV/hMPV cross-reactive human antibodies. One antibody, 5-1, potently neutralizes all tested viruses from the major subgroups of RSV and hMPV and provides protection against RSV and hMPV in a mouse challenge model. Structural analysis reveals that 5-1 utilizes an uncommon genetic signature to bind an epitope that spans sites Ø, II and V, defining a new mode of antibody cross-reactivity between RSV and hMPV F. These findings highlight the molecular and structural elements influencing RSV and hMPV cross-reactivity as well as the potential of antibody 5-1 for translational development., Competing Interests: DECELERATION OF INTERESTS A.A.A. and I.S.G. are listed as inventors on patents filed describing the antibodies discovered here. I.S.G. is listed as an inventor on patent applications for the LIBRA-seq technology. I.S.G. is a co-founder of AbSeek Bio. I.S.G. has served as a consultant for Sanofi. The Georgiev laboratory at VUMC has received unrelated funding from Merck and Takeda Pharmaceuticals. J.E.C. has served as a consultant for Luna Labs USA, Merck Sharp & Dohme Corporation, Emergent Biosolutions, a former member of the Scientific Advisory Boards of Gigagen (Grifols), of Meissa Vaccines, and BTG International, is founder of IDBiologics and receives royalties from UpToDate. The laboratory of J.E.C. received unrelated sponsored research agreements from AstraZeneca, Takeda Vaccines, and IDBiologics during the conduct of the study.

Throughout life, humans experience repeated exposure to viral antigens through infection and vaccination, resulting in the generation of diverse, antigen-specific antibody repertoires. A paramount feature of antibodies that enables their critical contributions in counteracting recurrent and novel pathogens, and consequently fostering their utility as valuable targets for therapeutic and vaccine development, is the exquisite specificity displayed against their target antigens. Yet, there is still limited understanding of the determinants of antibody-antigen specificity, particularly as a function of antibody sequence. In recent years, experimental characterization of antibody repertoires has led to novel insights into fundamental properties of antibody sequences but has been largely decoupled from at-scale antigen specificity analysis. Here, using the LIBRA-seq technology, we generated a large data set mapping antibody sequence to antigen specificity for thousands of B cells, by screening the repertoires of a set of healthy individuals against 20 viral antigens representing diverse pathogens of biomedical significance. Analysis uncovered virus-specific patterns in variable gene usage, gene pairing, somatic hypermutation, as well as the presence of convergent antiviral signatures across multiple individuals, including the presence of public antibody clonotypes. Notably, our results showed that, for B-cell receptors originating from different individuals but leveraging an identical combination of heavy and light chain variable genes, there is a specific CDRH3 identity threshold above which B cells appear to exclusively share the same antigen specificity. This finding provides a quantifiable measure of the relationship between antibody sequence and antigen specificity and further defines experimentally grounded criteria for defining public antibody clonality.IMPORTANCEThe B-cell compartment of the humoral immune system plays a critical role in the generation of antibodies upon new and repeated pathogen exposure. This study provides an unprecedented level of detail on the molecular characteristics of antibody repertoires that are specific to each of the different target pathogens studied here and provides empirical evidence in support of a 70% CDRH3 amino acid identity threshold in pairs of B cells encoded by identical IGHV:IGL(K)V genes, as a means of defining public clonality and therefore predicting B-cell antigen specificity in different individuals. This is of exceptional importance when leveraging public clonality as a method to annotate B-cell receptor data otherwise lacking antigen specificity information. Understanding the fundamental rules of antibody-antigen interactions can lead to transformative new approaches for the development of antibody therapeutics and vaccines against current and emerging viruses., Competing Interests: A.A.A.-S. and I.S.G. are listed as inventors on patents filed describing the antibodies discovered here. I.S.G. is listed as an inventor on patent applications for the LIBRA-seq technology. I.S.G. is a co-founder of AbSeek Bio. I.S.G. has served as a consultant for Sanofi. The Georgiev laboratory at VUMC has received unrelated funding from Merck and Takeda Pharmaceuticals.

A significant body of evidence indicates that climate change is influencing many aspects of avian ecology. Yet, how climate change is affecting, and is expected to influence some aspects of the breeding ecology of cavity-nesting birds remains uncertain. To explore the potential linkage between timing of first clutch, and the influence of ambient temperature on hatching success, we used Eastern Bluebird ( Sialia sialis ) nest records over a nine-year period from Alabama, USA. We investigated changes to annual clutch initiation dates, as well as variability in hatching success associated with ambient air temperatures during the incubation period. Using a simple linear model, we observed earlier annual egg laying dates over the nine years of this study with a difference of 24 days between earliest egg-laying date of the season. Daily temperature minima increased 2 °C across the nine-year time frame of this study. These data also indicate that Eastern Bluebird hatching success was the highest when mean ambient air temperature during incubation was between 19 °C and 24 °C (78%, as opposed to 69% and 68% above and below this temperature range, respectively). Our findings of increasing maxima, earlier maxima each year, and the lower minima of temperatures within our study area could expand the breadth of temperatures experienced by nesting Eastern Bluebirds possibly exposing them to temperatures outside of what promotes nesting success. These findings with a cavity-nesting bird highlight an optimal range of ambient temperatures associated with highest hatching success, conditions likely to be affected by climate change., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Human metapneumovirus (hMPV) is an important respiratory pathogen for which no licensed antivirals or vaccines exist. Single-domain antibodies represent promising antiviral biologics that can be easily produced and formatted. We describe the isolation and detailed characterization of two hMPV-neutralizing single-domain antibodies that are directed against the fusion protein F. One of these single-domain antibodies broadly neutralizes hMPV A and B strains, can prevent proteolytic maturation of F, and binds to an epitope in the F trimer interface. This suggests that hMPV pre-F undergoes trimer opening or "breathing" on infectious virions, exposing a vulnerable site for neutralizing antibodies. Finally, we show that this single-domain antibody, fused to a human IgG1 Fc, can protect cotton rats against hMPV replication, an important finding for potential future clinical applications., Competing Interests: This work was supported by a grant from Janssen Pharmaceuticals Inc. to X.S.

Human metapneumovirus (hMPV) is a major cause of acute respiratory infections in infants and older adults, for which no vaccines or therapeutics are available. The viral fusion (F) glycoprotein is required for entry and is the primary target of neutralizing antibodies; however, little is known about the humoral immune response generated from natural infection. Here, using prefusion-stabilized F proteins to interrogate memory B cells from two older adults, we obtain over 700 paired non-IgM antibody sequences representing 563 clonotypes, indicative of a highly polyclonal response. Characterization of 136 monoclonal antibodies reveals broad recognition of the protein surface, with potently neutralizing antibodies targeting each antigenic site. Cryo-EM studies further reveal two non-canonical sites and the molecular basis for recognition of the apex of hMPV F by two prefusion-specific neutralizing antibodies. Collectively, these results provide insight into the humoral response to hMPV infection in older adults and will help guide vaccine development., Competing Interests: Declaration of interests G.B., C.-L.H., E.C., J.N.R.-T., C.D.S., C.A.B., A.K., R.G., S.T.M., L.Z., D.C., T.-M.F., and J.M.D. are all current or former employees of Sanofi and may hold stock in Sanofi., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Human metapneumovirus (hMPV) is a leading cause of acute lower respiratory tract infections in high-risk populations, yet there are no vaccines or anti-viral therapies approved for the prevention or treatment of hMPV-associated disease. Here, we used a high-throughput single-cell technology to interrogate memory B cell responses to the hMPV fusion (F) glycoprotein in young adult and elderly donors. Across all donors, the neutralizing antibody response was primarily directed to epitopes expressed on both pre- and post-fusion F conformations. However, we identified rare, highly potent broadly neutralizing antibodies that recognize pre-fusion-specific epitopes and structurally characterized an antibody that targets a site of vulnerability at the pre-fusion F trimer apex. Additionally, monotherapy with neutralizing antibodies targeting three distinct antigenic sites provided robust protection against lower respiratory tract infection in a small animal model. This study provides promising monoclonal antibody candidates for passive immunoprophylaxis and informs the rational design of hMPV vaccine immunogens., Competing Interests: Declaration of interests C.G.R., E.S.E., J.C.G., A.Z.W., M.S., and L.M.W. are current or former employees of Adimab, LLC and may hold shares in Adimab, LLC. L.M.W. is an employee of Adagio Therapeutics Inc. and holds shares in Adagio Therapeutics Inc., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Respiratory syncytial virus (RSV) is a substantial cause of morbidity and mortality globally. A candidate RSV prefusion (pre-F)-stabilized subunit vaccine, DS-Cav1, has previously been shown to elicit potent and durable neutralizing activity in a phase 1 clinical trial in healthy adults. Here, we used fluorescently labeled probes and flow cytometry to evaluate the antigen specificity and phenotype of RSV F-specific B cells longitudinally after DS-Cav1 immunization. Peripheral blood mononuclear cells (PBMCs) collected at time points before the first immunization through the end of the trial at 44 weeks were assessed by flow cytometry. Our data demonstrate a rapid increase in the frequency of pre-F-specific IgG + and IgA + B cells after the first immunization and a modest increase after a second immunization at week 12. Nearly all F-specific B cells down-regulated CD21 and up-regulated the proliferation marker CD71 after the first immunization, with less pronounced activation after the second immunization. Memory B cells (CD27 + CD21 + ) specific for pre-F remained elevated above baseline at 44 weeks after vaccination. DS-Cav1 vaccination also activated human metapneumovirus (HMPV) cross-reactive B cells capable of binding prefusion-stabilized HMPV F protein and increased HMPV F-binding antibodies and neutralizing activity for HMPV in some participants. In summary, vaccination with RSV pre-F resulted in the expansion and activation of RSV and HMPV F-specific B cells that were maintained above baseline for at least 10 months and could contribute to long-term pneumovirus immunity.

Human metapneumovirus (hMPV) is a leading cause of morbidity and hospitalization among children worldwide, however, no vaccines or therapeutics are currently available for hMPV disease prevention and treatment. The hMPV fusion (F) protein is the sole target of neutralizing antibodies. To map the immunodominant epitopes on the hMPV F protein, we isolated a panel of human monoclonal antibodies (mAbs), and the mAbs were assessed for binding avidity, neutralization potency, and epitope specificity. We found the majority of the mAbs target diverse epitopes on the hMPV F protein, and we discovered multiple mAb binding approaches for antigenic site III. The most potent mAb, MPV467, which had picomolar potency, was examined in prophylactic and therapeutic mouse challenge studies, and MPV467 limited virus replication in mouse lungs when administered 24 h before or 72 h after viral infection. We determined the structure of MPV467 in complex with the hMPV F protein using cryo-electron microscopy to a resolution of 3.3 Å, which revealed a complex novel prefusion-specific epitope overlapping antigenic sites II and V on a single protomer. Overall, our data reveal insights into the immunodominant antigenic epitopes on the hMPV F protein, identify a mAb therapy for hMPV F disease prevention and treatment, and provide the discovery of a prefusion-specific epitope on the hMPV F protein.

The human metapneumovirus (hMPV) fusion (F) protein is essential for viral entry and is a key target of neutralizing antibodies and vaccine development. The prefusion conformation is thought to be the optimal vaccine antigen, but previously described prefusion F proteins expressed poorly and were not well stabilized. Here, we use structures of hMPV F to guide the design of 42 variants containing stabilizing substitutions. Through combinatorial addition of disulfide bonds, cavity-filling substitutions, and improved electrostatic interactions, we describe a prefusion-stabilized F protein (DS-CavEs2) that expresses at 15 mg/L and has a melting temperature of 71.9 °C. Crystal structures of two prefusion-stabilized hMPV F variants reveal that antigenic surfaces are largely unperturbed. Importantly, immunization of mice with DS-CavEs2 elicits significantly higher neutralizing antibody titers against hMPV A1 and B1 viruses than postfusion F. The improved properties of DS-CavEs2 will advance the development of hMPV vaccines and the isolation of therapeutic antibodies., (© 2022. The Author(s).)

Tropical cyclones drive coastal ecosystem dynamics, and their frequency, intensity, and spatial distribution are predicted to shift with climate change. Patterns of resistance and resilience were synthesized for 4138 ecosystem time series from n = 26 storms occurring between 1985 and 2018 in the Northern Hemisphere to predict how coastal ecosystems will respond to future disturbance regimes. Data were grouped by ecosystems (fresh water, salt water, terrestrial, and wetland) and response categories (biogeochemistry, hydrography, mobile biota, sedentary fauna, and vascular plants). We observed a repeated pattern of trade-offs between resistance and resilience across analyses. These patterns are likely the outcomes of evolutionary adaptation, they conform to disturbance theories, and they indicate that consistent rules may govern ecosystem susceptibility to tropical cyclones.

Filanesib is a first-in-class kinesin spindle protein inhibitor which demonstrated safety and encouraging activity in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma in a preliminary analysis of dose-escalation phase results. This multicenter study included first a dose-escalation phase to determine maximum tolerated dose of two schedules of filanesib, bortezomib, and dexamethasone and a subsequent dose-expansion phase using the maximum tolerated doses. In the dose-expansion phase, 28 patients were evaluable for safety and efficacy. The most common grade ≥3 adverse events were neutropenia (21%) and anemia (18%), which were noncumulative and reversible, and hypertension (18%). The overall response rate was 43% with median duration of response not yet reached (range, 2.8-23.7+ months) with median follow-up of 6.3 months. A post hoc analysis incorporated 29 dose-escalation phase patients who received therapeutic filanesib doses, with an overall response rate of 39% and median duration of response of 18.0 months among the 57 total patients with median progression-free survival of 8.5 months. Notably, the PFS of high risk patients was comparable at 8.5 months, driven by the patients with 1q21 gain, characterized by increased MCL-1 expression, with a PFS of 9.1 months versus 3.5 months for the remainder of high risk patients. Patients with t(11;14) also had an encouraging PFS of 15.0 months. The combination of filanesib, bortezomib, and dexamethasone continues to show safety and encouraging activity in relapsed/refractory multiple myeloma, particularly in those patients with 1q21 gain and t(11;14)., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Respiratory syncytial virus (RSV) is a major cause of childhood medically attended respiratory infection (MARI)., Methods: We conducted a randomized, double-blind, placebo-controlled phase 3 trial in 1154 preterm infants of 1 or 2 doses of suptavumab, a human monoclonal antibody that can bind and block a conserved epitope on RSV A and B subtypes, for the prevention of RSV MARI. The primary endpoint was proportion of subjects with RSV-confirmed hospitalizations or outpatient lower respiratory tract infection (LRTI)., Results: There were no significant differences between primary endpoint rates (8.1%, placebo; 7.7%, 1-dose; 9.3%, 2-dose). Suptavumab prevented RSV A infections (relative risks, .38; 95% confidence interval [CI], .14-1.05 in the 1-dose group and .39 [95% CI, .14-1.07] in the 2-dose group; nominal significance of combined suptavumab group vs placebo; P = .0499), while increasing the rate of RSV B infections (relative risk 1.36 [95% CI, .73-2.56] in the 1-dose group and 1.69 [95% CI, .92-3.08] in the 2-dose group; nominal significance of combined suptavumab group vs placebo; P = .12). Sequenced RSV isolates demonstrated no suptavumab epitope changes in RSV A isolates, while all RSV B isolates had 2-amino acid substitution in the suptavumab epitope that led to loss of neutralization activity. Treatment emergent adverse events were balanced across treatment groups., Conclusions: Suptavumab did not reduce overall RSV hospitalizations or outpatient LRTI because of a newly circulating mutant strain of RSV B. Genetic variation in circulating RSV strains will continue to challenge prevention efforts., Clinical Trials Registration: NCT02325791., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Aim: The present work aims to morphologically and molecularly characterize an Eimeria sp. recovered from an adult, captive barred owl Strix varia in Mississippi, USA. While the owl was shedding oocysts, no clinical signs of coccidiosis were observed., Materials and Methods: Oocysts collected from a barred owl, S. varia were isolated from feces by fecal flotation and characterized by light microscopy. The oocysts were allowed to sporulate in K 2 Cr 2 O 7 for 7 days and measured for comparison with previously described Eimeria species. Genomic DNA was extracted from measured oocysts and the cytochrome c oxidase subunit 1 mitochondrial gene was amplified and sequenced for comparison and phylogenetic analyses with publicly available sequence data., Results: Oocysts collected from S. varia were morphologically and molecularly consistent with all previous accounts of Eimeria megabubonis from the great horned owl Bubo virginianus and morphologically consistent with the only account of Eimeria varia from S. varia. Phylogenetic analyses grouped the E. megabubonis sequence from the present study with previously reported sequences from E. megabubonis., Conclusion: Morphological and molecular data from oocysts collected in this study reveal S. varia is a host for E. megabubonis. Agreement between current data, morphological and molecular data of E. megabubonis, and morphological data from the original description of E. varia indicates E. varia is a junior synonym of E. megabubonis.

Millions of tons of plastic enter the environment every year, where much of it concentrates in environmental sinks such as tidal marshes. With prior studies documenting harm to marine fauna caused by this plastic pollution, the need to understand how this novel type of pollution affects estuarine fauna is great. Yet, research on the fate and uptake of plastic pollutants in estuarine ecosystems is sparse. Therefore, we quantified plastic prevalence and ingestion by two species of resident marsh bird, Clapper Rails (Rallus crepitans) and Seaside Sparrows (Ammospiza maritima), in coastal marsh ecosystems within Mississippi. We detected microplastics (plastics smaller than 5 mm) in 64% of marsh sediment samples, 83% of Clapper Rail and 69% of Seaside Sparrow proventriculus samples. Dominant types of microplastics detected in sediment and bird samples were fibers. This study provides the first evidence of microplastic ingestion by marsh birds and its distribution in coastal marshes within Mississippi., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

An effective vaccine for respiratory syncytial virus (RSV) is an unrealized public health goal. A single dose of the prefusion-stabilized fusion (F) glycoprotein subunit vaccine (DS-Cav1) substantially increases serum-neutralizing activity in healthy adults. We sought to determine whether DS-Cav1 vaccination induces a repertoire mirroring the pre-existing diversity from natural infection or whether antibody lineages targeting specific epitopes predominate. We evaluated RSV F-specific B cell responses before and after vaccination in six participants using complementary B cell sequencing methodologies and identified 555 clonal lineages. DS-Cav1-induced lineages recognized the prefusion conformation of F (pre-F) and were genetically diverse. Expressed antibodies recognized all six antigenic sites on the pre-F trimer. We identified 34 public clonotypes, and structural analysis of two antibodies from a predominant clonotype revealed a common mode of recognition. Thus, vaccination with DS-Cav1 generates a diverse polyclonal response targeting the antigenic sites on pre-F, supporting the development and advanced testing of pre-F-based vaccines against RSV., Competing Interests: Declaration of interests B.S.G., J.S.M., and P.D.K. are inventors on a patent entitled “Prefusion RSV F proteins and their use” (US Patent No. 9738689)., (Published by Elsevier Inc.)

Neuronal growth regulator 1 (NEGR1) and neurotrimin (NTM) are abundant cell-surface proteins found in the brain and form part of the IgLON (Immunoglobulin LSAMP, OBCAM, Neurotrimin) family. In humans, NEGR1 is implicated in obesity and mental disorders, while NTM is linked to intelligence and cognitive function. IgLONs dimerize homophilically and heterophilically, and they are thought to shape synaptic connections and neural circuits by acting in trans (spanning cellular junctions) and/or in cis (at the same side of a junction). Here, we reveal homodimeric structures of NEGR1 and NTM. They assemble into V-shaped complexes via their Ig1 domains, and disruption of the Ig1-Ig1 interface abolishes dimerization in solution. A hydrophobic ridge from one Ig1 domain inserts into a hydrophobic pocket from the opposing Ig1 domain producing an interaction interface that is highly conserved among IgLONs but remarkably plastic structurally. Given the high degree of sequence conservation at the interaction interface, we tested whether different IgLONs could elicit the same biological effect in vivo. In a small-scale study administering different soluble IgLONs directly into the brain and monitoring feeding, only NEGR1 altered food intake significantly. Taking NEGR1 as a prototype, our studies thus indicate that while IgLONs share a conserved mode of interaction and are able to bind each other as homomers and heteromers, they are structurally plastic and can exert unique biological action., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Low-grade weirs placed within agricultural drainage ditches in the Lower Mississippi Alluvial Valley can be used as a management practice to enhance nitrogen removal. The addition of organic carbon amendments within ditches that contain weirs could further increase nitrogen removal. Through repeated trials, changes in NO 3 - -N concentration between inflow and outflow were variable in the ditch without weirs, while only decreases in concentration were observed in ditches with weirs. Significant differences in NO 3 - -N concentrations were observed between treatments, with greater removal of NO 3 - -N observed in dissolved organic carbon treatments compared to control and particulate organic carbon treatments. At medium- and high-flow rates, respectively, dissolved organic carbon treatments resulted in greater NO 3 - -N concentration decreases of 31.6% and 27.1% compared to 19% and 11.6% in particulate organic carbon treatments and 18.6% and 17.2% in control treatments. Significant effects of weirs and sampling date on nirS, nirK, nosZ, and 16S rRNA gene abundances were observed. Observed increases in NO 3 - -N removal with organic carbon amendments, provides support for continued investigation on improving the efficacy of organic carbon amendments as a best management practice for NO 3 - -N removal in agricultural drainage ditches. PRACTITIONER POINTS: Dissolved organic carbon amendments increased nitrate-nitrogen removal. Only decreases in nitrate-nitrogen concentration were observed in ditches with weirs. Increasing flow rate did not affect nitrate-nitrogen removal. Abundance of denitrification-performing microbes likely did not affect N removal. Lack of anaerobic soil conditions and short residence time reduced nitrate-N removal., (© 2019 Water Environment Federation.)

Aims: To assess pathological changes associated with natural infections of the trematode Odhneriotrema incommodum in wild-caught American alligators Alligator mississippiensis and assess potential first intermediate hosts., Materials and Methods: Tongues from two wild-caught alligators were obtained from a commercial alligator processor in Port Gibson, Mississippi, USA. Tongues were subjected to gross parasitological examination and routine histological assessment. Eggs were expressed from adult trematodes collected from these tongues into distilled water, where they hatched into infectious miracidia. The snails Planorbella trivolvis, Physa gyrina, and Biomphalaria havanensis were exposed to these miracidia and observed for cercarial emergence for 200 days post-exposure., Results: Histological assessment of alligator tongues revealed marked hemorrhage, necrosis, presence of bacteria, and inflammation at sites of Odhneriotrema incommodum attachment, differing from previous histological reports from controlled experimental studies. Cercarial emergence was not observed in snails exposed to infectious miracidia., Conclusions: Wild-caught alligators infected with Odhneriotrema incommodum exhibit more severe pathology than was previously noted from experimentally infected alligators. This adverse pathology may be associated with microbes present in eutrophic natural habitats that are absent from controlled environments used in experimental exposures. Impacts of this parasite in wild alligator populations are likely underestimated and damage associated with parasite attachment could increase host susceptibility to secondary infections. Given the importance of alligators as game animals and sustained demand for alligator products, further study into the role of O. incommodum on alligator health is warranted. Results of snail exposures to miracidia suggest these snail species are not suitable first intermediate hosts for this trematode and the true first intermediate host of O. incommodum remains unknown.

This data article provides the methods and procedures followed to collect and analyse soil, vegetation and bird data on three different treatment islands in Guntersville Reservoir, Alabama. Samples were collected from randomly selected plot points from islands that were placed into three different treatment types: Colony (currently occupied by Double-crested Cormorants) ( Phalacrocorax auritus ; n = 5), Historic (historically occupied by cormorants and currently abandoned; n = 3) and Reference (never occupied by cormorants; n = 4). We compared vegetation and tree metrics such as structure and diversity, as well as soil chemistry and bird diversity and communities among islands within Guntersville Reservoir. These data document for the first time that we are aware of the long-term effects of soil chemistry changes, vegetation changes, and impacts to avian diversity, in temperate forest ecosystems, by cormorant colonies. All data is associated with the recent article by Veum et al. [1] and provided here as raw data.

In the Intensive Care Unit (ICU), family members experience psychological and spiritual distress as they cope with fear, grief, and medical decisions for patients. The study team developed and pilot tested a semistructured chaplain intervention that included proactive contact and spiritual assessment, interventions, and documentation. An interdisciplinary team developed the intervention, the Spiritual Care Assessment and Intervention (SCAI) Framework. Three chaplains delivered the intervention to surrogates in two ICUs. There were 25 of 73 eligible patient/surrogate dyads enrolled. Surrogates had a mean age of 57.6, were 84% female and 32% African American. The majority (84%) were Protestant. All received at least one chaplain visit and 19 received three visits. All agreed they felt supported by the chaplains, and qualitative comments showed spiritual and emotional support were valued. A semistructured spiritual care intervention for ICU surrogates is feasible and acceptable. Future work is needed to demonstrate the intervention improves outcomes for surrogates and patients.

While nine nominal species of Eimeria Schneider, 1875 have been described from strigiform birds, molecular sequence data are not available for any of these species. In the present study, oöcysts of a coccidian were isolated by faecal flotation from the lower intestinal contents of an opportunistically collected, recently deceased great horned owl Bubo virginianus (Gmelin), sporulated in potassium dichromate, and subjected to morphological and molecular characterisation. Comparisons of morphological data with previous accounts of Eimeria spp. from owls were consistent with Eimeria megabubonis Upton, Campbell, Weigel & McKown, 1990. Novel molecular data for the 18S ribosomal RNA gene region and the mitochondrial cytochrome c oxidase subunit 1 gene are provided. The results of phylogenetic analysis based on concatenated sequence data from these regions are presented and implications for the evolutionary history of Eimeria are discussed.

Species distribution modeling often involves high-dimensional environmental data. Large amounts of data and multicollinearity among covariates impose challenges to statistical models in variable selection for reliable inferences of the effects of environmental factors on the spatial distribution of species. Few studies have evaluated and compared the performance of multiple machine learning (ML) models in handling multicollinearity. Here, we assessed the effectiveness of removal of correlated covariates and regularization to cope with multicollinearity in ML models for habitat suitability. Three machine learning algorithms maximum entropy (MaxEnt), random forests (RFs), and support vector machines (SVMs) were applied to the original data (OD) of 27 landscape variables, reduced data (RD) with 14 highly correlated covariates being removed, and 15 principal components (PC) of the OD accounting for 90% of the original variability. The performance of the three ML models was measured with the area under the curve and continuous Boyce index. We collected 663 nonduplicated presence locations of Eastern wild turkeys ( Meleagris gallopavo silvestris ) across the state of Mississippi, United States. Of the total locations, 453 locations separated by a distance of ≥2 km were used to train the three ML algorithms on the OD, RD, and PC data, respectively. The remaining 210 locations were used to validate the trained ML models to measure ML performance. Three ML models had excellent performance on the RD and PC data. MaxEnt and SVMs had good performance on the OD data, indicating the adequacy of regularization of the default setting for multicollinearity. Weak learning of RFs through bagging appeared to alleviate multicollinearity and resulted in excellent performance on the OD data. Regularization of ML algorithms may help exploratory studies of the effects of environmental factors on the spatial distribution and habitat suitability of wildlife., Competing Interests: The authors have no conflict of interest related to this work.

Novel molecular data from both mitochondrial ( cytochrome c oxidase subunit 1) and ribosomal regions ( 18S, ITS1-5.8S, ITS2, and 28S) are provided for Sebekia mississippiensis Overstreet, Self, & Vliet, 1985 , a pentastome infecting the American alligator, Alligator mississippiensis Daudin, 1801, and the spotted gar, Lepisosteus oculatus Winchell, 1864. Adult and nymphal pentastomes are described from the lungs and liver of the type host, A. mississippiensis, collected from Mississippi, while additional nymphs are described from the esophageal lining of L. oculatus specimens collected from Louisiana. This sequencing data will facilitate more accurate identification of various life cycle stages of S. mississippiensis, enabling future work to resolve many ambiguities in the literature regarding this species. Additionally, histopathological data are provided from both the definitive and intermediate hosts.

In November 2017, oöcysts of the coccidian Eimeria macyi Wheat, 1975 were isolated from the faeces of a single eastern red bat Lasiurus borealis Müller in Lowndes County, Mississippi, USA. Sporulated oöcysts, morphologically consistent with previous accounts of E. macyi in other chiropterans, were spherical to sub-spherical in shape with a highly mamillated outer wall that appears bi-layered. Oöcysts allowed to sporulate in 2.5% potassium dichromate at ambient temperature (c.23°C) for 7 days were 17-25 × 15-20 (20.7 × 17.9) µm. Micropyle and oöcyst residuum were absent with one to two polar granules scattered among sporocysts. The four ovoid sporocysts were 7-12 × 6-8 (9.9 × 7.1) µm. Stieda bodies were prominent and sub-Stieda bodies were present. Two sporozoites were reflexed within each sporocyst. Nuclear 18S rRNA gene, plastid 23S rRNA gene and mitochondrial cytochrome c oxidase subunit 1 (cox1) gene were sequenced from sporulated oöcysts and compared to other molecular data of Eimeria spp. from rodent and chiropteran hosts. No sequence data in the NCBI database matched E. macyi. Phylogenetic analyses of the sequence data of the 18S rRNA and 23S rRNA genes placed E. macyi within a clade containing Eimeria spp. from rodents and basal to a clade populated by sequences derived from Eimeria spp. of rodents and bats. This account represents a new host record of E. macyi in an eastern red bat and a new geographic locality. Additionally, the cox1 sequence data of Eimeria macyi represents the first mitochondrial sequence of an Eimeria sp. in bats.

Agricultural non-point sources of nutrients and sediments have caused eutrophication and other water quality issues in aquatic and marine ecosystems, such as the annual occurrence of hypoxia in the Gulf of Mexico. Management practices have been implemented adjacent to and in agricultural drainage ditches to promote their wetland characteristics and functions, including reduction of nitrogen, phosphorus, and sediment losses downstream. This review: (1) summarized studies examining changes in nutrient and total suspended solid concentrations and loads associated with management practices in drainage ditches (i.e., riser and slotted pipes, two-stage ditches, vegetated ditches, low-grade weirs, and organic carbon amendments) with emphasis on the Lower Mississippi Alluvial Valley, (2) quantified management system effects on nutrient and total suspended solid concentrations and loads and, (3) identified information gaps regarding water quality associated with these management practices and research needs in this area. In general, management practices used in drainage ditches at times reduced losses of total suspended solids, N, and P. However, management practices were often ineffective during storm events that were uncommon and intense in duration and volume, although these types of events could increase in frequency and intensity with climate change. Studies on combined effects of management practices on drainage ditch water quality, along with research towards improved nutrient and sediment reduction efficiency during intense storm events are urgently needed.

Background: Filanesib (ARRY-520) is a highly selective inhibitor of kinesin spindle protein, which has demonstrated preclinical antimyeloma activity., Methods: This open-label Phase 1/2 study determined the maximum tolerated dose of Filanesib administered on Days 1 and 2 of 14-Day Cycles in patients with multiple myeloma (MM) and included expansion cohorts with and without dexamethasone (40 mg/week). Patients in the dose-escalation (N = 31) and Phase 2 single-agent (N = 32) cohorts had received prior bortezomib as well as prior thalidomide and/or lenalidomide. Patients in the Phase 2 Filanesib plus dexamethasone cohort (N = 55) had received prior alkylator therapy and had disease refractory to lenalidomide, bortezomib, and dexamethasone. Prophylactic filgrastim was incorporated during dose escalation and was used throughout Phase 2., Results: Patients in each cohort had received a median of ≥6 prior therapies. The most common dose-limiting toxicities were febrile neutropenia and mucosal inflammation. In Phase 2, Grade 3 and 4 cytopenias were reported in approximately 50% of patients. Nonhematologic toxicities were infrequent. Phase 2 response rates (partial responses or better) were 16% (single agent) and 15% (Filanesib plus dexamethasone). All responding patients had low baseline levels of α1-acid glycoprotein, a potential selective biomarker., Conclusions: Filanesib 1.50 mg/m 2 /day administered with prophylactic filgrastim has a manageable safety profile and encouraging activity in heavily pretreated patients This study is registered at www.clinicaltrials.gov as NCT00821249. Cancer 2017;123:4617-4630. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Based on specimens collected from harvested American alligator Alligator mississippiensis Daudin, 1801 in Mississippi, USA, novel molecular data for both nuclear ribosomal genes (18S, ITS1-5.8S, ITS2, and 28S) and mitochondrial genes (cytochrome c oxidase subunit 1 and nicotinamide adenine dinucleotide dehydrogenase subunit 1) are provided for Odhneriotrema incommodum (Leidy, 1856), a trematode of the family Clinostomidae Lühe, 1901 infecting A. mississippiensis and the Florida spotted gar Lepisosteus platyrhincus DeKay, 1842. This represents the first sequencing data available for the genus Odhneriotrema and the subfamily Nephrocephalinae Travassos, 1928. Additionally, the results of phylogenetic analyses, additional morphometric data, a photomicrograph, and a line drawing supporting the present identification of O. incommodum are provided. These data will aid in elucidating the life cycle of O. incommodum through molecular identification of larval stages as well as understanding the evolutionary history of Clinostomidae and its subfamilies. Implications for the currently accepted organization of the Clinostomidae are discussed.

Background: Filanesib is a kinesin spindle protein inhibitor that has demonstrated encouraging activity in patients with recurrent/refractory multiple myeloma. Preclinical synergy with bortezomib was the rationale for the current phase 1 study., Methods: The current study was a multicenter study with an initial dose-escalation phase to determine the maximum tolerated dose of 2 schedules of filanesib plus bortezomib with and without dexamethasone, followed by a dose-expansion phase., Results: With the addition of prophylactic filgastrim, the maximum planned dose was attained: 1.3 mg/m 2 /day of bortezomib plus 40 mg of dexamethasone on days 1, 8, and 15 of a 28-day cycle, with filanesib given intravenously either at a dose of 1.5 mg/m 2 /day (schedule 1: days 1, 2, 15, and 16) or 3 mg/m 2 /day (schedule 2: days 1 and 15). The most common adverse events (assessed for severity using version 4.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events) were transient, noncumulative neutropenia and thrombocytopenia with grade 3/4 events reported in 44% (16% in cycle 1 with filgastrim) and 29% of patients, respectively. A low (≤11%) overall rate of nonhematological grade 3/4 toxicity was observed. With a median of 3 prior lines of therapy and 56% of patients with disease that was refractory to proteasome inhibitors, the overall response rate was 20% (55 patients), and was 29% in 14 patients with proteasome inhibitors-refractory disease receiving filanesib at a dose of ≥1.25 mg/m 2 (duration of response, 5.2 to ≥21.2 months)., Conclusions: The current phase 1 study established a dosing schedule for the combination of these agents that demonstrated a favorable safety profile with a low incidence of nonhematologic toxicity and manageable hematologic toxicity. The combination of filanesib, bortezomib, and dexamethasone appears to have durable activity in patients with recurrent/refractory multiple myeloma. Cancer 2016;122:3327-3335. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

The 1972 Clean Water Act was passed to protect chemical, physical, and biological integrity of United States' waters. The U.S. Environmental Protection Agency and U.S. Army Corps of Engineers codified a new "waters of the United States" rule on June 29, 2015, because several Supreme Court case decisions caused confusion with the existing rule. Climate change could affect this rule through connectivity between groundwater and surface waters; floodplain waters and the 100-year floodplain; changes in jurisdictional status; and sea level rise on coastal ecosystems. Four approaches are discussed for handling these implications: (1) "Wait and see"; (2) changes to the rule; (3) use guidance documents; (4) Congress statutorily defining "waters of the United States." The approach chosen should be legally defensible and achieved in a timely fashion to provide protection to "waters of the United States" in proactive consideration of scientifically documented effects of climate change on aquatic ecosystems.

Guppies (Poecilia reticulata) are models for understanding the interplay between natural and sexual selection. In particular, predation has been implicated as a major force affecting female sexual preferences, male mating tactics and the level of sperm competition. When predation is high, females typically reduce their preferences for showy males and engage more in antipredator behaviours, whereas males exploit these changes by switching from sexual displays to forced matings. These patterns are thought to account for the relatively high levels of multiple paternity in high-predation populations compared to low-predation populations. Here, we assess the possible evolutionary consequences of these patterns by asking whether variation in sperm traits reflect differences in predation intensity among four pairs of Trinidadian populations: four that experience relatively low levels of predation from a gape-limited predator and four that experience relatively high levels of predation from a variety of piscivores. We found that males in high-predation populations had faster swimming sperm with longer midpieces compared to males in low-predation populations. However, we found no differences among males in high- and low-predation populations with respect to sperm number, sperm head length, flagellum length and total sperm length.

1. Synchronized mass production of seed crops, such as acorns, produces a resource pulse that may have far-reaching consequences for songbird populations through its effects on avian predators. Seed production in these forests represents only the first of several pulsed events. Secondary pulses emerge as mast-consuming rodents numerically respond to seed production and tertiary pulses emerge as generalist predators, such as raptors, numerically respond to rodents. In turn, these two groups reduce nest productivity and juvenile survivorship 1 and 2 years, respectively, after the initial pulse in seed production. 2. At our study site in south-eastern New York, USA, autumn acorn abundance (primary pulse) largely determines rodent abundance (secondary pulse) the following spring. We tested the hypotheses that the population dynamics of a shrub-nesting passerine (wood thrush Hylocichla mustelina), is influenced by rodents through the: (a) direct effect of predation by rodents; (b) indirect effect of rodents on the abundance of raptors (tertiary pulse); and (c) indirect effect of rodent abundance on raptor diet. The latter specifically hypothesizes that a crash in the rodent population in the wake of region-wide failure of acorn production leads to an extreme diet shift in raptors that increases post-fledging mortality in birds. 3. We conducted a 3-year study to examine variation in wood thrush nest success and fledgling survival, using radio telemetry, across a pulse of rodent abundance (i.e. low, medium and high). We also updated and reanalysed regional wood thrush population growth rates as a function of the annual variation in rodent abundance. 4. Fledgling survivorship, but not nest success, varied in relation to annual rodent abundance. Raptors and eastern chipmunks Tamias striatus were the most commonly identified predators on fledglings. Fledgling survivorship was greatest at intermediate rodent abundance consistent with a shift in raptor diet. Regional rate of wood thrush population growth showed a unimodal relationship with rodent abundance, peaking during years with intermediate rodent abundance. This unimodal pattern was due to wood thrush population growth rates near or below zero during rodent population crashes. 5. The telemetry study, pattern of regional abundance and synchronized population dynamics of coexisting thrushes suggest a common mechanism of behavioural changes in raptors in response to declines in rodent prey, which in turn affects thrush population dynamics.

To assess geographic distributions of elements in the Arctic we compared essential and non-essential elements in the livers of polar bears (Ursus maritimus) collected from five regions within Canada in 2002, in Alaska between 1994 and 1999 and from the northwest and east coasts of Greenland between 1988 and 2000. As, Hg, Pb and Se varied with age, and Co and Zn with gender, which limited spatial comparisons across all populations to Cd, which was highest in Greenland bears. Collectively, geographic relationships appeared similar to past studies with little change in concentration over time in Canada and Greenland for most elements; Hg and Se were higher in some Canadian populations in 2002 as compared to 1982 and 1984. Concentrations of most elements in the polar bears did not exceed toxicity thresholds, although Cd and Hg exceeded levels correlated with the formation of hepatic lesions in laboratory animals.