Integrating data types to estimate spatial patterns of avian migration across the Western Hemisphere.

For many avian species, spatial migration patterns remain largely undescribed, especially across hemispheric extents. Recent advancements in tracking technologies and high-resolution species distribution models (i.e., eBird Status and Trends products) provide new insights into migratory bird movements and offer a promising opportunity for integrating independent data sources to describe avian migration. Here, we present a three-stage modeling framework for estimating spatial patterns of avian migration. First, we integrate tracking and band re-encounter data to quantify migratory connectivity, defined as the relative proportions of individuals migrating between breeding and nonbreeding regions. Next, we use estimated connectivity proportions along with eBird occurrence probabilities to produce probabilistic least-cost path (LCP) indices. In a final step, we use generalized additive mixed models (GAMMs) both to evaluate the ability of LCP indices to accurately predict (i.e., as a covariate) observed locations derived from tracking and band re-encounter data sets versus pseudo-absence locations during migratory periods and to create a fully integrated (i.e., eBird occurrence, LCP, and tracking/band re-encounter data) spatial prediction index for mapping species-specific seasonal migrations. To illustrate this approach, we apply this framework to describe seasonal migrations of 12 bird species across the Western Hemisphere during pre- and postbreeding migratory periods (i.e., spring and fall, respectively). We found that including LCP indices with eBird occurrence in GAMMs generally improved the ability to accurately predict observed migratory locations compared to models with eBird occurrence alone. Using three performance metrics, the eBird + LCP model demonstrated equivalent or superior fit relative to the eBird-only model for 22 of 24 species-season GAMMs. In particular, the integrated index filled in spatial gaps for species with over-water movements and those that migrated over land where there were few eBird sightings and, thus, low predictive ability of eBird occurrence probabilities (e.g., Amazonian rainforest in South America). This methodology of combining individual-based seasonal movement data with temporally dynamic species distribution models provides a comprehensive approach to integrating multiple data types to describe broad-scale spatial patterns of animal movement. Further development and customization of this approach will continue to advance knowledge about the full annual cycle and conservation of migratory birds.

Operative Results of Mitral Valve Repair and Replacement in Chronic Ischaemic Mitral Valve Regurgitation.

BACKGROUND: Ischaemic mitral regurgitation (IMR) carries significant morbidity and mortality. Surgical management includes coronary artery bypass surgery alone or concomitant with mitral valve repair or replacement. There is ongoing debate regarding the appropriate approach to the mitral valve in relation to long-term outcomes. This review examines our early and late follow-up, with operative and echocardiographic outcomes for mitral valve repair and mitral replacement for chronic IMR. METHODS: A retrospective review was performed on prospectively collected data of 119 consecutive patients who either underwent mitral repair (n=101) or mitral replacement (n=18) for chronic IMR at Prince Henry and The Prince of Wales hospitals in Sydney between 1999-2016. All patients had pre and postoperative transthoracic echocardiograms. Follow-up echocardiographic data was obtained from the most recent clinical appointment. Follow-up mortality outcomes were obtained with ethics approval from the Australian National Death Index (NDI). RESULTS: There was no statistical difference between cardiopulmonary bypass (CPB) time, cross-clamp time, time spent in intensive care unit (ICU) and time to discharge between cohorts. The replacement cohort was noted to have higher preoperative pulmonary artery (PA) pressures and a higher severity of IMR. Seven (7) deaths were in the mitral valve (MV) repair group within 30 days (6.9%) and three deaths in the MV replacement group within 30 days (16.7%). Echocardiographic follow-up was complete in 78% of the MV repair cohort at an average of 4.06±2.66 years, and 73% complete in the MV replacement cohort at an average of 6.09±4.3 years. Three (3) patients had prior MV repair before MV replacement early at days zero and 17, and late at 8 years respectively. Follow-up echocardiography showed mitral regurgitation (MR) in the mitral valve repair cohort as ≤ mild in 83.5% and ≤ trivial in 35.6%. In the MV replacement cohort MR ≤ mild in 100% and ≤ trivial in 82% with no moderate or severe MR. Preoperative tricuspid regurgitation (TR) and a flexible annuloplasty were predictive of an MR grade > mild in the repair cohort at discharge. Five-year (5-year) survival for the repair cohort was 85% with a mean follow-up time of 7.1±3.83 years. For the replacement cohort, five-year survival was 77.8% with a mean follow-up time of 5.35±1.54 years. CONCLUSIONS: Mitral valve repair and replacement for chronic IMR has acceptable mortality, reintervention rates and excellent postoperative echocardiographic degrees of IMR in this cohort. Further evaluation is required into quality of life post intervention for IMR and of preoperative predictive factors of significant MR postoperatively to help guide the appropriate choice of treatment. The presence of preoperative tricuspid regurgitation of moderate grade or higher, and the use of a flexible annuloplasty may indicate patients more likely to have a higher grade of MR at follow-up following mitral valve repair in patients with IMR.

Prevention of Sternal Wound Infections by use of a Surgical Incision Management System: First Reported Australian Case Series.

BACKGROUND: Sternal wound infections are considered a costly and potentially devastating consequence of the median sternotomy in cardiothoracic surgery. Surgical incision management employs the technique of applying a closed, negative pressure vacuum dressing to a closed wound. Several studies have demonstrated a reduction in sternal wound infections using this system. METHODS: A retrospective audit of cases receiving surgical incision management demonstrated a statistically significant reduction in sternal wound infections against a predicted rate. RESULTS: Of the 62 patients identified, only one was complicated by a sternal wound infection with the greatest reduction seen in the high-risk infection group. CONCLUSIONS: Although smaller in size, the results compared well to trials conducted in larger European and US centres. Although not advocating surgical incision management for routine use, it should be considered on patients considered high-risk for sternal wound infection, such as diabetics, the elderly and the obese.

Identification of an avian polyomavirus associated with Adélie penguins (Pygoscelis adeliae).

Little is known about viruses associated with Antarctic animals, although they are probably widespread. We recovered a novel polyomavirus from Adélie penguin (Pygoscelis adeliae) faecal matter sampled in a subcolony at Cape Royds, Ross Island, Antarctica. The 4988 nt Adélie penguin polyomavirus (AdPyV) has a typical polyomavirus genome organization with three ORFs that encoded capsid proteins on the one strand and two non-structural protein-coding ORFs on the complementary strand. The genome of AdPyV shared ~60 % pairwise identity with all avipolyomaviruses. Maximum-likelihood phylogenetic analysis of the large T-antigen (T-Ag) amino acid sequences showed that the T-Ag of AdPyV clustered with those of avipolyomaviruses, sharing between 48 and 52 % identities. Only three viruses associated with Adélie penguins have been identified at a genomic level, avian influenza virus subtype H11N2 from the Antarctic Peninsula and, respectively, Pygoscelis adeliae papillomavirus and AdPyV from capes Crozier and Royds on Ross Island.

Successful Giant Thymic Cyst Removal: Case Report and Review of the Literature.

Giant thymic cysts are a rare clinical entity evolving from smaller benign thymic cysts over many years. Benign thymic cysts account for approximately 3% of all mediastinal masses. There is a paucity of literature regarding benign thymic cyst management, especially when dealing with giant cysts. This can lead to potential confusion amongst clinicians on how to best treat these patients. We report the successful diagnosis and treatment of a 76 year-old female with a giant, benign thymic cyst. This cyst was discovered incidentally and after consultation of the literature it was found management strategies regarding this condition are scarce. After careful consideration of surgical principles, patient preference and potential complications of a conservative approach, the successful surgical removal of a 1.8 kg cyst took place. The patient improved symptomatically with improved exercise tolerance and lung function tests. This case demonstrates the benefits of giant thymic cyst removal thus confirming diagnosis, reducing potential serious complications and improving patient quality of life.

A novel papillomavirus in Adélie penguin (Pygoscelis adeliae) faeces sampled at the Cape Crozier colony, Antarctica.

Papillomaviruses are epitheliotropic viruses that have circular dsDNA genomes encapsidated in non-enveloped virions. They have been found to infect a variety of mammals, reptiles and birds, but so far they have not been found in amphibians. Using a next-generation sequencing de novo assembly contig-informed recovery, we cloned and Sanger sequenced the complete genome of a novel papillomavirus from the faecal matter of Adélie penguins (Pygoscelis adeliae) nesting on Ross Island, Antarctica. The genome had all the usual features of a papillomavirus and an E9 ORF encoding a protein of unknown function that is found in all avian papillomaviruses to date. This novel papillomavirus genome shared ~60 % pairwise identity with the genomes of the other three known avian papillomaviruses: Fringilla coelebs papillomavirus 1 (FcPV1), Francolinus leucoscepus papillomavirus 1 (FlPV1) and Psittacus erithacus papillomavirus 1. Pairwise identity analysis and phylogenetic analysis of the major capsid protein gene clearly indicated that it represents a novel species, which we named Pygoscelis adeliae papillomavirus 1 (PaCV1). No evidence of recombination was detected in the genome of PaCV1, but we did detect a recombinant region (119 nt) in the E6 gene of FlPV1 with the recombinant region being derived from ancestral FcPV1-like sequences. Previously only paramyxoviruses, orthomyxoviruses and avian pox viruses have been genetically identified in penguins; however, the majority of penguin viral identifications have been based on serology or histology. This is the first report, to our knowledge, of a papillomavirus associated with a penguin species.

Aberrant immune programming in neutrophils in cystic fibrosis.

Cystic fibrosis is a life-shortening genetic disorder, caused by mutations in the gene that encodes cystic fibrosis transmembrane-conductance regulator, a cAMP-activated chloride and bicarbonate channel. Persistent neutrophilic inflammation is a major contributor to cystic fibrosis lung disease. However, how cystic fibrosis transmembrane-conductance regulator loss of function leads to excessive inflammation and its clinical sequela remains incompletely understood. In this study, neutrophils from F508del-CF and healthy control participants were compared for gene transcription. We found that cystic fibrosis circulating neutrophils have a prematurely primed basal state with significantly higher scores for activation, chemotaxis, immune signaling, and pattern recognition. Such an irregular basal state appeared not related to the blood environment and was also observed in neutrophils derived from the F508del-CF HL-60 cell line, indicating an innate characteristic of the phenotype. Lipopolysaccharides (LPS) stimulation drastically shifted the transcriptional landscape of healthy control neutrophils toward a robust immune response; however, cystic fibrosis neutrophils were immune-exhausted, reflected by abnormal cell aging and fate determination in gene programming. Moreover, cystic fibrosis sputum neutrophils differed significantly from cystic fibrosis circulating neutrophils in gene transcription with increased inflammatory response, aging, apoptosis, and necrosis, suggesting additional environmental influences on the neutrophils in cystic fibrosis lungs. Taken together, our data indicate that loss of cystic fibrosis transmembrane-conductance regulator function has intrinsic effects on neutrophil immune programming, leading to premature priming and dysregulated response to challenge.

Bronchial haemangioma: exceptionally rare cause of haemoptysis.

Bronchial haemangioma is an exceptionally rare cause of haemoptysis in the adult. There are currently less than 10 recorded cases in the literature. Airway haemangiomas are generally seen in infants with coexistent cutaneous haemangiomas. The incidence of bronchial haemangioma in adults remains unknown. This case reports the diagnosis and treatment of a bronchial haemangioma in a 56 year-old male presenting with a one-month history of haemoptysis. Bronchial haemangioma diagnosis was confirmed and excision performed by bronchoscopy without complication. Bronchial haemangioma should be a considered differential diagnosis in the presence of meaningful haemoptysis when an endoluminal lesion is visualised on computed tomography scan. This case also demonstrates that bronchial haemangiomas can be successfully removed via bronchoscopy with minimal risk and discomfort to the patient.

Loss of CFTR function in macrophages alters the cell transcriptional program and delays lung resolution of inflammation.

Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the CF Transmembrane-conductance Regulator (CFTR) gene. The most severe pathologies of CF occur in the lung, manifesting as chronic bacterial infection, persistent neutrophilic inflammation, and mucopurulent airway obstruction. Despite increasing knowledge of the CF primary defect and the resulting clinical sequelae, the relationship between the CFTR loss of function and the neutrophilic inflammation remains incompletely understood. Here, we report that loss of CFTR function in macrophages causes extended lung inflammation. After intratracheal inoculation with Pseudomonas aeruginosa, mice with a macrophage-specific Cftr-knockout (Mac-CF) were able to mount an effective host defense to clear the bacterial infection. However, three days post-inoculation, Mac-CF lungs demonstrated significantly more neutrophil infiltration and higher levels of inflammatory cytokines, suggesting that Mac-CF mice had a slower resolution of inflammation. Single-cell RNA sequencing revealed that absence of CFTR in the macrophages altered the cell transcriptional program, affecting the cell inflammatory and immune responses, antioxidant system, and mitochondrial respiration. Thus, loss of CFTR function in macrophages influences cell homeostasis, leading to a dysregulated cellular response to infection that may exacerbate CF lung disease.

ABERRANT IMMUNE PROGRAMMING IN NEUTROPHILS IN CYSTIC FIBROSIS.

Cystic fibrosis (CF) is a life-shortening genetic disorder, caused by mutations in the gene that encodes Cystic Fibrosis Transmembrane-conductance Regulator (CFTR), a cAMP-activated chloride and bicarbonate channel. Although multiple organ systems can be affected, CF lung disease claims the most morbidity and mortality due to chronic bacterial infection, persistent neutrophilic inflammation, and mucopurulent airway obstruction. Despite the clear predominance of neutrophils in these pathologies, how CFTR loss-of-function affects these cells per se remains incompletely understood. Here, we report the profiling and comparing of transcriptional signatures of peripheral blood neutrophils from CF participants and healthy human controls (HC) at the single-cell level. Circulating CF neutrophils had an aberrant basal state with significantly higher scores for activation, chemotaxis, immune signaling, and pattern recognition, suggesting that CF neutrophils in blood are prematurely primed. Such an abnormal basal state was also observed in neutrophils derived from an F508del-CF HL-60 cell line, indicating an innate characteristic of the phenotype. LPS stimulation drastically shifted the transcriptional landscape of HC circulating neutrophils towards a robust immune response, however, CF neutrophils were immune-exhausted. Moreover, CF blood neutrophils differed significantly from CF sputum neutrophils in gene programming with respect to neutrophil activation and aging, as well as inflammatory signaling, highlighting additional environmental influences on the neutrophils in CF lungs. Taken together, loss of CFTR function has intrinsic effects on neutrophil immune programming that leads to premature priming and dysregulated response to challenge.

Neutrophil defect and lung pathogen selection in cystic fibrosis.

Cystic fibrosis is a life-threatening genetic disorder caused by mutations in the CFTR chloride channel. Clinically, over 90% of patients with cystic fibrosis succumb to pulmonary complications precipitated by chronic bacterial infections, predominantly by Pseudomonas aeruginosa and Staphylococcus aureus. Despite the well-characterized gene defect and clearly defined clinical sequelae of cystic fibrosis, the critical link between the chloride channel defect and the host defense failure against these specific pathogens has not been established. Previous research from us and others has uncovered that neutrophils from patients with cystic fibrosis are defective in phagosomal production of hypochlorous acid, a potent microbicidal oxidant. Here we report our studies to investigate if this defect in hypochlorous acid production provides P. aeruginosa and S. aureus with a selective advantage in cystic fibrosis lungs. A polymicrobial mixture of cystic fibrosis pathogens (P. aeruginosa and S. aureus) and non-cystic fibrosis pathogens (Streptococcus pneumoniae, Klebsiella pneumoniae, and Escherichia coli) was exposed to varied concentrations of hypochlorous acid. The cystic fibrosis pathogens withstood higher concentrations of hypochlorous acid than did the non-cystic fibrosis pathogens. Neutrophils derived from F508del-CFTR HL-60 cells killed P. aeruginosa less efficiently than did the wild-type counterparts in the polymicrobial setting. After intratracheal challenge in wild-type and cystic fibrosis mice, the cystic fibrosis pathogens outcompeted the non-cystic fibrosis pathogens and exhibited greater survival in the cystic fibrosis lungs. Taken together, these data indicate that reduced hypochlorous acid production due to the absence of CFTR function creates an environment in cystic fibrosis neutrophils that provides a survival advantage to specific microbes-namely, S. aureus and P. aeruginosa-in the cystic fibrosis lungs.

A modified Hai-Murphy model of uterine smooth muscle contraction.

We extend and analyze the Wang and Politi modified Hai-Murphy model of smooth muscle cell contractions to capture uterine muscle cell response to variations in intracellular calcium concentrations. This model is used to estimate values of unknown parameters in uterine smooth muscle cell cross-bridging. Uterine motility is responsible for carrying out important processes throughout all phases of the nonpregnant female reproductive cycle, including sperm transport, menstruation, and embryo implantation. The modified Hai-Murphy partial differential equation model accounts for the displacement of myosin cross-bridge heads relative to their binding sites. This model was originally developed for the study of airway contractions; we now extended it for use in modeling nonisometric uterine contractions. Our extended model incorporates cross-bridge position and contractile velocity into the original model, resulting in more accurate modeling of the initial stages of contraction and modeling nonisometric contractions. Numerical simulations show that the contraction rate in our extended model is faster than the original Hai-Murphy model. These simulations provide quantitative estimates for the increased level of responsiveness of our extended model to intracellular calcium concentrations. The extended model and new parameter estimates for the cross-bridging can be coupled with uterine flow models to advance our understanding of embryonic motility and intrauterine flow.

Comparison of Proportion of Elevated Carcinoembryonic Antigen Levels in Patients With Appendiceal and Colorectal Adenocarcinoma: A Systematic Review and Meta-analysis.

BACKGROUND/AIM: The proportion of patients with liver metastases in patients with appendiceal versus colorectal adenocarcinomas was 3.1 percent and 24 percent, respectively, in our peritonectomy centre. From our internal analyses, carcinoembryonic antigen (CEA) was potentially involved. A hypothesis was proposed regarding the natural progression of appendiceal adenocarcinoma. To support this, a systematic review and meta-analysis were performed to examine whether there was a difference in the proportion of patients with an elevated CEA in appendiceal versus colorectal adenocarcinoma patients in the current literature. MATERIALS AND METHODS: Medline (PubMed), EMBASE (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature, Clinicaltrials.gov, Web of Science, and Google Scholar were searched. All studies involving patients with appendiceal and/or colorectal adenocarcinoma were eligible. Data were analysed by grouping appendiceal and colorectal adenocarcinoma in separate meta-analyses, and then comparing their weighted proportions of elevated CEA. Principal summary measures were weighted proportions of patients with elevated CEA. RESULTS: From the initial identification of 1,928 articles, 136 articles were included in the final synthesis. Ninety-two articles were included in the meta-analysis. Proportions of appendiceal and colorectal adenocarcinoma with elevated CEA were 56% (95%CI=47-65%) and 42% (95%CI=38-46%), respectively (p=0.0001). CONCLUSION: Patients with appendiceal adenocarcinoma had a higher proportion of CEA than those with colorectal adenocarcinoma. Future studies should focus on the several aspects of CEA presented in patients with appendiceal adenocarcinoma. This could provide treatments for patients with colorectal adenocarcinoma by preventing the development of liver metastases.

Corrigendum: Short-Chain Alcohols Upregulate GILZ Gene Expression and Attenuate LPS-Induced Septic Immune Response.

[This corrects the article DOI: 10.3389/fimmu.2020.00053.].

Cftr deletion in mouse epithelial and immune cells differentially influence the intestinal microbiota.

Cystic fibrosis (CF) is a life-threatening genetic disorder, caused by mutations in the CF transmembrane-conductance regulator gene (cftr) that encodes CFTR, a cAMP-activated chloride and bicarbonate channel. Clinically, CF lung disease dominates the adult patient population. However, its gastrointestinal illness claims the early morbidity and mortality, manifesting as intestinal dysbiosis, inflammation and obstruction. As CF is widely accepted as a disease of epithelial dysfunction, it is unknown whether CFTR loss-of-function in immune cells contributes to these clinical outcomes. Using cftr genetic knockout and bone marrow transplantation mouse models, we performed 16S rRNA gene sequencing of the intestinal microbes. Here we show that cftr deletion in both epithelial and immune cells collectively influence the intestinal microbiota. However, the immune defect is a major factor determining the dysbiosis in the small intestine, while the epithelial defect largely influences that in the large intestine. This finding revises the current concept by suggesting that CF epithelial defect and immune defect play differential roles in CF intestinal disease.

Great egret (Ardea alba) habitat selection and foraging behavior in a temperate estuary: Comparing natural wetlands to areas with shellfish aquaculture.

Movement by animals to obtain resources and avoid predation often depends on natural cycles, and human alteration of the landscape may disrupt or enhance the utility of different habitats or resources to animals through the phases of these cycles. We studied habitat selection by GPS/accelerometer-tagged great egrets (Ardea alba) foraging in areas with shellfish aquaculture infrastructure and adjacent natural wetlands, while accounting for tide-based changes in water depth. We used integrated step selection analysis to test the prediction that egrets would express stronger selection for natural wetlands (eelgrass, tidal marsh, and other tidal wetlands) than for shellfish aquaculture areas. We also evaluated differences in foraging behavior among shellfish aquaculture areas and natural wetlands by comparing speed travelled (estimated from distance between GPS locations) and energy expended (Overall Dynamic Body Acceleration) while foraging. We found evidence for stronger overall habitat selection for eelgrass than for shellfish aquaculture areas, with results conditional on water depth: egrets used shellfish aquaculture areas, but only within a much narrower range of water depths than they used eelgrass and other natural wetlands. We found only slight differences in our metrics of foraging behavior among shellfish aquaculture areas and natural wetlands. Our results suggest that although great egrets appear to perceive or experience shellfish aquaculture areas as suitable foraging habitat during some conditions, those areas provide less foraging opportunity throughout tidal cycles than natural wetlands. Thus, expanding the footprint of shellfish aquaculture into additional intertidal areas may reduce foraging opportunities for great egrets across the range of tidal cycles. Over longer time scales, the ways in which natural wetlands and shellfish aquaculture areas adapt to rising sea levels (either through passive processes or active management) may change the ratios of these wetland types and consequently change the overall value of Tomales Bay to foraging great egrets.

Short-Chain Alcohols Upregulate GILZ Gene Expression and Attenuate LPS-Induced Septic Immune Response.

Alcohol differentially affects human health, depending on the pattern of exposure. Moderate intake provides beneficial mood modulation and an anti-inflammatory effect, while excessive consumption leads to immunosuppression and various alcohol use disorders. The mechanism underlying this bi-phasic action mode of alcohol has not been clearly defined. Our previous publication demonstrated that ethanol, in the absence of glucocorticoids (GCs), induces expression of Glucocorticoid-Induced Leucine Zipper (GILZ), a key molecule that transduces GC anti-inflammatory effect through a non-canonical activation of glucocorticoid receptor (1). Here we report that similar short-chain alcohols, such as ethanol, propanol and isopropanol, share the same property of upregulating GILZ gene expression, and blunt cell inflammatory response in vitro. When mice were exposed to these alcohols, GILZ gene expression in immune cells was augmented in a dose-dependent manner. Monocytes and neutrophils were most affected. The short-chain alcohols suppressed host inflammatory response to lipopolysaccharide (LPS) and significantly reduced LPS-induced mortality. Intriguingly, propanol and isopropanol displayed more potent protection than ethanol at the same dose. Inhibition of ethanol metabolism enhanced the ethanol protective effect, suggesting that it is ethanol, not its derivatives or metabolites, that induces immune suppression. Taken together, short-chain alcohols per se upregulate GILZ gene expression and provide immune protection against LPS toxicity, suggesting a potential measure to counter LPS septic shock in a resource limited situation.

Nephron-Sparing Robotic Radiosurgical Therapy for Primary Renal Cell Carcinoma: Single-Institution Experience and Review of the Literature.

PURPOSE: We report our single-institution stereotactic body radiation therapy (SBRT) experience on stage I renal cancer with prospectively collected toxicity and efficacy data. METHODS AND MATERIALS: A total of 21 patients with solitary renal tumors, including 14 surgical candidates who refused surgery (66%), were treated with SBRT. Histologic confirmation was obtained on all patients before treatment; 2 had transitional cell carcinoma and 19 had renal cell carcinoma. The median age was 71 years (range, 58-88). Nearly all patients received 48 Gy in 3 fractions. RESULTS: The median follow-up was 78 months (range, 5-107). At 5 years post treatment, the local tumor control rate was 100%. Tumor size decreased by a median value of 5.3% at 1 year post treatment, 15.6% at 2 years post treatment, and 15.4% at 5 years post treatment. Glomerular filtration rate had decreased by a median value of 1.5% at 1 year post treatment, 7.0% at 2 years post treatment, and 14.2% at 5 years post treatment. Three patients experienced grade 1 toxicity; no other treatment-related adverse effects were reported. CONCLUSIONS: SBRT is a promising noninvasive treatment in the management of primary renal cell carcinoma, with evolving clinical evidence demonstrating encouraging results with respect to local control and toxicity.

Myeloid CFTR loss-of-function causes persistent neutrophilic inflammation in cystic fibrosis.

Persistent neutrophilic inflammation is a hallmark of cystic fibrosis (CF). However, the mechanisms underlying this outstanding pathology remain incompletely understood. Here, we report that CFTR in myeloid immune cells plays a pivotal role in control of neutrophilic inflammation. Myeloid CFTR-Knockout (Mye-Cftr-/-) mice and congenic wild-type (WT) mice were challenged peritoneally with zymosan particles at different doses, creating aseptic peritonitis with varied severity. A high-dose challenge resulted in significantly higher mortality in Mye-Cftr-/- mice, indicating an intrinsic defect in host control of inflammation in mice whose myeloid cells lack CF. The low-dose challenge demonstrated an impaired resolution of inflammation in Mye-Cftr-/- mice, reflected by a significant overproduction of proinflammatory cytokines, including neutrophil chemokines MIP-2 and KC, and sustained accumulation of neutrophils. Tracing neutrophil mobilization in vivo demonstrated that myeloid CF mice recruited significantly more neutrophils than did WT mice. Pulmonary challenge with zymosan elicited exuberant inflammation in the lung and recapitulated the findings from peritoneal challenge. To determine the major type of cell that was primarily responsible for the over-recruitment of neutrophils, we purified and cultured ex vivo zymosan-elicited peritoneal neutrophils and macrophages. The CF neutrophils produced significantly more MIP-2 than did the WT counterparts, and peripheral blood neutrophils isolated from myeloid CF mice also produced significantly more MIP-2 after zymosan stimulation in vitro. These data altogether suggest that CFTR dysfunction in myeloid immune cells, especially neutrophils, leads to hyperinflammation and excessive neutrophil mobilization in the absence of infection. Thus, dysregulated inflammation secondary to abnormal or absent CFTR in myeloid cells may underlie the clinically observed neutrophilic inflammation in CF.

Effects of drought on the abundance and distribution of non-breeding shorebirds in central California, USA.

Conservation of migratory species requires anticipating the potential impacts of extreme climatic events, such as extreme drought. During drought, reduced habitat availability for shorebirds creates the potential for changes in their abundance and distribution, in part because many species are highly mobile and rely on networks of interior and coastal habitats. Understanding how shorebirds responded to a recent drought cycle that peaked from 2013 to 2015 in central California, USA, will help optimize management of wetlands and fresh water for wildlife. In the Central Valley, a vast interior region that is characterized by a mosaic of wetlands and agricultural lands, we found 22% and 29% decreases in the annual abundance of shorebirds during periods of 3-year drought (2013-2015) and 2-year extreme drought (2014-2015), respectively, when compared to non-drought years. Lower abundance of shorebirds coincided with significant decreases in the mean proportion flooded of survey units (7% and 9%, respectively) that were reliant on fresh water. Drought was associated with lower abundance within both the interior Central Valley and coastal San Francisco Bay for greater and lesser yellowlegs (Tringa melanoleuca and T. flavipes) and long- and short-billed dowitchers (Limnodromus scolopaceus and L. griseus). Only dunlins (Calidris alpina) had patterns of abundance that suggested substantial shifts in distribution between the Central Valley and coastal regions of San Francisco Bay and Point Reyes. Our results indicate that drought has the potential to reduce, at least temporally, shorebird populations and flooded habitat in the Central Valley, and the ability to respond to drought by taking advantage of nearby coastal habitats may limit the long-term effects of drought on some species. Successful conservation strategies must balance the impacts of reduced habitat availability at interior sites with the ability of some migratory shorebirds to adapt rapidly to shifting distributions of resources.