Current And Future Land Use Around A Nationwide Protected Area Network

Land-use change around protected areas can reduce their effective size and limit their ability to conserve biodiversity because land-use change alters ecological processes and the ability of organisms to move freely among protected areas. The goal of our analysis was to inform conservation planning efforts for a nationwide network of protected lands by predicting future land use change. We evaluated the relative effect of three economic policy scenarios on land use surrounding the U.S. Fish and Wildlife Service\u27s National Wildlife Refuges. We predicted changes for three land-use classes (forest/range, crop/pasture, and urban) by 2051. Our results showed an increase in forest/range lands (by 1.9% to 4.7% depending on the scenario), a decrease in crop/pasture between 15.2% and 23.1%, and a substantial increase in urban land use between 28.5% and 57.0%. The magnitude of land-use change differed strongly among different USFWS administrative regions, with the most change in the Upper Midwestern US (approximately 30%), and the Southeastern and Northeastern US (25%), and the rest of the U.S. between 15 and 20%. Among our scenarios, changes in land use were similar, with the exception of our restricted-urban-growth\u27\u27 scenario, which resulted in noticeably different rates of change. This demonstrates that it will likely be difficult to influence land-use change patterns with national policies and that understanding regional land-use dynamics is critical for effective management and planning of protected lands throughout the U.S

Current and Future Land Use around a Nationwide Protected Area Network

Land-use change around protected areas can reduce their effective size and limit their ability to conserve biodiversity because land-use change alters ecological processes and the ability of organisms to move freely among protected areas. The goal of our analysis was to inform conservation planning efforts for a nationwide network of protected lands by predicting future land use change. We evaluated the relative effect of three economic policy scenarios on land use surrounding the U.S. Fish and Wildlife Service’s National Wildlife Refuges. We predicted changes for three land-use classes (forest/range, crop/pasture, and urban) by 2051. Our results showed an increase in forest/range lands (by 1.9% to 4.7% depending on the scenario), a decrease in crop/pasture between 15.2% and 23.1%, and a substantial increase in urban land use between 28.5% and 57.0%. The magnitude of land-use change differed strongly among different USFWS administrative regions, with the most change in the Upper Midwestern US (approximately 30%), and the Southeastern and Northeastern US (25%), and the rest of the U.S. between 15 and 20%. Among our scenarios, changes in land use were similar, with the exception of our ‘‘restricted-urban-growth’’ scenario, which resulted in noticeably different rates of change. This demonstrates that it will likely be difficult to influence land-use change patterns with national policies and that understanding regional land-use dynamics is critical for effective management and planning of protected lands throughout the U.S

Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial.

BACKGROUND: Myeloma causes profound immunodeficiency and recurrent, serious infections. Around 5500 new cases of myeloma are diagnosed per year in the UK, and a quarter of patients will have a serious infection within 3 months of diagnosis. We aimed to assess whether patients newly diagnosed with myeloma benefit from antibiotic prophylaxis to prevent infection, and to investigate the effect on antibiotic-resistant organism carriage and health care-associated infections in patients with newly diagnosed myeloma. METHODS: TEAMM was a prospective, multicentre, double-blind, placebo-controlled randomised trial in patients aged 21 years and older with newly diagnosed myeloma in 93 UK hospitals. All enrolled patients were within 14 days of starting active myeloma treatment. We randomly assigned patients (1:1) to levofloxacin or placebo with a computerised minimisation algorithm. Allocation was stratified by centre, estimated glomerular filtration rate, and intention to proceed to high-dose chemotherapy with autologous stem cell transplantation. All investigators, patients, laboratory, and trial co-ordination staff were masked to the treatment allocation. Patients were given 500 mg of levofloxacin (two 250 mg tablets), orally once daily for 12 weeks, or placebo tablets (two tablets, orally once daily for 12 weeks), with dose reduction according to estimated glomerular filtration rate every 4 weeks. Follow-up visits occurred every 4 weeks up to week 16, and at 1 year. The primary outcome was time to first febrile episode or death from all causes within the first 12 weeks of trial treatment. All randomised patients were included in an intention-to-treat analysis of the primary endpoint. This study is registered with the ISRCTN registry, number ISRCTN51731976, and the EU Clinical Trials Register, number 2011-000366-35. FINDINGS: Between Aug 15, 2012, and April 29, 2016, we enrolled and randomly assigned 977 patients to receive levofloxacin prophylaxis (489 patients) or placebo (488 patients). Median follow-up was 12 months (IQR 8-13). 95 (19%) first febrile episodes or deaths occurred in 489 patients in the levofloxacin group versus 134 (27%) in 488 patients in the placebo group (hazard ratio 0·66, 95% CI 0·51-0·86; p=0·0018. 597 serious adverse events were reported up to 16 weeks from the start of trial treatment (308 [52%] of which were in the levofloxacin group and 289 [48%] of which were in the placebo group). Serious adverse events were similar between the two groups except for five episodes (1%) of mostly reversible tendonitis in the levofloxacin group. INTERPRETATION: Addition of prophylactic levofloxacin to active myeloma treatment during the first 12 weeks of therapy significantly reduced febrile episodes and deaths compared with placebo without increasing health care-associated infections. These results suggest that prophylactic levofloxacin could be used for patients with newly diagnosed myeloma undergoing anti-myeloma therapy. FUNDING: UK National Institute for Health Research

Genome-wide Association Study of Platelet Count Identifies Ancestry-Specific Loci in Hispanic/Latino Americans

Platelets play an essential role in hemostasis and thrombosis. We performed a genome-wide association study of platelet count in 12,491 participants of the Hispanic Community Health Study/Study of Latinos by using a mixed-model method that accounts for admixture and family relationships. We discovered and replicated associations with five genes (ACTN1, ETV7, GABBR1-MOG, MEF2C, and ZBTB9-BAK1). Our strongest association was with Amerindian-specific variant rs117672662 (p value = 1.16 × 10−28) in ACTN1, a gene implicated in congenital macrothrombocytopenia. rs117672662 exhibited allelic differences in transcriptional activity and protein binding in hematopoietic cells. Our results underscore the value of diverse populations to extend insights into the allelic architecture of complex traits

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Statistical Methods for the Analysis of Microbiome Data

Thesis (Ph.D.)--University of Washington, 2018The human microbiome plays a vital role in maintaining health, and imbalances in the microbiome are associated with a wide variety of diseases. Understanding whether and how the microbiome is associated with particular health conditions is a focus of many modern microbiome studies, with the hope that a deeper understanding of these associations may lead to more effective prevention and treatment regimens. However, how best to analyze data from microbiome profiling studies remains unclear. The high dimensionality, compositional nature, intrinsic biological structure, and limited availability of samples pose substantial statistical challenges. To face these challenges, we propose novel analytic approaches based on sparse penalized regression strategies and distance-based global association analysis. Most distance-based methods for global microbiome association analysis are restricted to simple dichotomous or quantitative outcomes, but more complex outcomes are increasingly common in microbiome studies. In the first part of this dissertation, we introduce two distance-based methods for the analysis of entire microbial communities in modern microbiome studies. We develop a kernel machine regression-based score test for association between the microbiome and censored time-to-event outcomes. We then propose a novel longitudinal measure of dissimilarity that summarizes changes in the microbiome across time and compares these changes between subjects. Since this dissimilarity may be incorporated into any distance-based analysis framework, it is a highly flexible tool for applying a wide variety of distance-based analyses in longitudinal studies. Identification of associated taxa and detection of predictive microbial signatures are key to translation of microbiome studies. In the second part of this dissertation, we present two penalized regression methods for estimation and prediction with high-dimensional compositional data. Because phylogenetic similarity between bacteria often corresponds to shared functions, our first contribution is to incorporate phylogenetic structure into a penalized regression model for constrained data. We then propose a model that exploits phylogenetic structure to use partial information in the setting of differing feature sets between model-building and prediction datasets. We evaluate the performance of these methods through extensive simulation studies and apply them to studies investigating the association of graft-versus-host disease or body mass index with the gut microbiome

Impact of Data and Study Characteristics on Microbiome Volatility Estimates

The human microbiome is a dynamic community of bacteria, viruses, fungi, and other microorganisms. Both the composition of the microbiome (the microbes that are present and their relative abundances) and the temporal variability of the microbiome (the magnitude of changes in their composition across time, called volatility) has been associated with human health. However, the effect of unbalanced sampling intervals and differential read depth on the estimates of microbiome volatility has not been thoroughly assessed. Using four publicly available gut and vaginal microbiome time series, we subsampled the datasets to several sampling intervals and read depths and then compared additive, multiplicative, centered log ratio (CLR)-based, qualitative, and distance-based measures of microbiome volatility between the conditions. We find that longer sampling intervals are associated with larger quantitative measures of change (particularly for common taxa), but not with qualitative measures of change or distance-based volatility quantification. A lower sequencing read depth is associated with smaller multiplicative, CLR-based, and qualitative measures of change (particularly for less common taxa). Strategic subsampling may serve as a useful sensitivity analysis in unbalanced longitudinal studies investigating clinical associations with microbiome volatility

The Loss Of Forest Birds Habitats Under Different Land Use Policies As Projected By A Coupled Ecological-econometric Model

Land use is driven by socio-economic factors that must be understood in order to mitigate habitat loss. Econometric land-use models describe how land use is affected by socio-economic factors, such as financial returns to different uses of land, and they can be linked to biological models to provide new insight for conservation. Our goal was to evaluate the effects of future land use change on the habitat of forest breeding bird species in northern Wisconsin. Specifically, we estimated the effects of land use change on the amount of habitat available and compared the effects of economic policy scenarios on bird habitat. To do this, we coupled a spatially-explicit econometric model of land use change on private lands with models of northern Wisconsin forest bird potential habitat, comparing a 50-yr baseline projection with a scenario providing incentives for forest growth and a high urban growth scenario. The baseline scenario suggests an average of 438,705 ha of forest lost (10%), with 1.9% of that saved under the Forest Incentive scenario, and a 1.6% greater loss for the Urban Growth scenario. Under baseline projections boreal birds experienced the least amount of habitat loss (2-3%), and deciduous forest birds the most (6-8%). For some species, the projected loss of habitat exacerbates ongoing long-term declining population trend. Coupled economic-ecological models can be used to evaluate alternative incentive programs and to explore the complex interactions between policy, land use change, and broad spatial scale ecological processes that are highly relevant to conservation

Polyinosinic acid enhances delivery of adenovirus vectors in vivo by preventing sequestration in liver macrophages

Adenovirus is among the preferred vectors for gene therapy because of its superior in vivo gene-transfer efficiency. However, upon systemic administration, adenovirus is preferentially sequestered by the liver, resulting in reduced adenovirus-mediated transgene expression in targeted tissues. In the liver, Kupffer cells are responsible for adenovirus degradation and contribute to the inflammatory response. As scavenger receptors present on Kupffer cells are responsible for the elimination of blood-borne pathogens, we investigated the possible implication of these receptors in the clearance of the adenovirus vector. Polyinosinic acid [poly(I)], a scavenger receptor A ligand, was analysed for its capability to inhibit adenovirus uptake specifically in macrophages. In in vitro studies, the addition of poly(I) before virus infection resulted in a specific inhibition of adenovirus-induced gene expression in a J774 macrophage cell line and in primary Kupffer cells. In in vivo experiments, pre-administration of poly(I) caused a 10-fold transient increase in the number of adenovirus particles circulating in the blood. As a consequence, transgene expression levels measured in different tissues were enhanced (by 5- to 15-fold) compared with those in animals that did not receive poly(I). Finally, necrosis of Kupffer cells, which normally occurs as a consequence of systemic adenovirus administration, was prevented by the use of poly(I). No toxicity, as measured by liver-enzyme levels, was observed after poly(I) treatment. From our data, we conclude that poly(I) can prevent adenovirus sequestration by liver macrophages. These results imply that, by inhibiting adenovirus uptake by Kupffer cells, it is possible to reduce the dose of the viral vector to diminish the liver-toxicity effect and to improve the level of transgene expression in target tissues. In systemic gene-therapy applications, this will have great impact on the development of targeted adenoviral vectors