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1.
J Dairy Sci ; 103(4): 3874-3881, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32113754

ABSTRACT

Management decisions can be informed by near-real-time data streams to improve the economics of the farm and to positively benefit the overall health of a dairy herd or the larger environment. Decision support tools can use data management services and analytics to exploit data streams from farm and other economic, health, and agricultural sources. We will describe a decision support tool that couples data analytics tools to underlying cow, herd, and economic data with an application programming interface. This interface allows the user to interact with a collection of dairy applications without fully exposing the intricacies of the underlying system model and understand the effects of different decisions on outputs of interest. The collection of these applications will form the basis of the Dairy Brain decision support system, which will provide management suggestions to farmers at a single animal or farm level. Dairy operations data will be gathered, cleaned, organized, and disseminated through an agricultural data hub, exploiting newly developed ontologies for integration of multiple data sources. Models of feed efficiency, culling, or other dairy operations (such as large capital expenditures, outsourcing opportunities, and interactions with regulators) form the basis of analytical approaches, operationalized via tools that help secure information and control uncertainties. The applications will be independently generated to provide flexibility, and use tools and modeling approaches from the data science, simulation, machine learning, and optimization disciplines to provide specific recommendations to decision makers. The Dairy Brain is a decision support system that couples data analytics tools with a suite of applications that integrate cow, herd, and economic data to inform management, operational, and animal health improving practices. Research challenges that remain include dealing with increased variability as predictions go from herd or pen level down to individual cow level and choosing the appropriate tool or technique to deal with a specific problem.


Subject(s)
Dairying/methods , Decision Making , Agriculture/economics , Agriculture/methods , Animals , Cattle , Dairying/economics , Data Science , Decision Support Techniques , Farmers , Female , User-Computer Interface
2.
PLoS Comput Biol ; 14(2): e1006010, 2018 02.
Article in English | MEDLINE | ID: mdl-29451895

ABSTRACT

Microbes may maximize the number of daughter cells per time or per amount of nutrients consumed. These two strategies correspond, respectively, to the use of enzyme-efficient or substrate-efficient metabolic pathways. In reality, fast growth is often associated with wasteful, yield-inefficient metabolism, and a general thermodynamic trade-off between growth rate and biomass yield has been proposed to explain this. We studied growth rate/yield trade-offs by using a novel modeling framework, Enzyme-Flux Cost Minimization (EFCM) and by assuming that the growth rate depends directly on the enzyme investment per rate of biomass production. In a comprehensive mathematical model of core metabolism in E. coli, we screened all elementary flux modes leading to cell synthesis, characterized them by the growth rates and yields they provide, and studied the shape of the resulting rate/yield Pareto front. By varying the model parameters, we found that the rate/yield trade-off is not universal, but depends on metabolic kinetics and environmental conditions. A prominent trade-off emerges under oxygen-limited growth, where yield-inefficient pathways support a 2-to-3 times higher growth rate than yield-efficient pathways. EFCM can be widely used to predict optimal metabolic states and growth rates under varying nutrient levels, perturbations of enzyme parameters, and single or multiple gene knockouts.


Subject(s)
Enzymes/chemistry , Escherichia coli/enzymology , Escherichia coli/growth & development , Metabolic Networks and Pathways , Systems Biology , Biochemical Phenomena , Biomass , Glucose/chemistry , Kinetics , Models, Biological , Models, Statistical , Oxygen/chemistry , Thermodynamics
3.
Glob Chang Biol ; 24(8): 3862-3872, 2018 08.
Article in English | MEDLINE | ID: mdl-29654612

ABSTRACT

Conservation practitioners face difficult choices in apportioning limited resources between rare species (to ensure their existence) and common species (to ensure their abundance and ecosystem contributions). We quantified the opportunity costs of conserving rare species of migratory fishes in the context of removing dams and retrofitting road culverts across 1,883 tributaries of the North American Great Lakes. Our optimization models show that maximizing total habitat gains across species can be very efficient in terms of benefits achieved per dollar spent, but disproportionately benefits common species. Conservation approaches that target rare species, or that ensure some benefits for every species (i.e., complementarity) enable strategic allocation of resources among species but reduce aggregate habitat gains. Thus, small habitat gains for the rarest species necessarily come at the expense of more than 20 times as much habitat for common ones. These opportunity costs are likely to occur in many ecosystems because range limits and conservation costs often vary widely among species. Given that common species worldwide are declining more rapidly than rare ones within major taxa, our findings provide incentive for triage among multiple worthy conservation targets.


Subject(s)
Biodiversity , Conservation of Natural Resources/economics , Fishes/classification , Animals , Endangered Species , Lakes
4.
Ecol Appl ; 28(6): 1494-1502, 2018 09.
Article in English | MEDLINE | ID: mdl-29885265

ABSTRACT

A hallmark of industrialization is the construction of dams for water management and roads for transportation, leading to fragmentation of aquatic ecosystems. Many nations are striving to address both maintenance backlogs and mitigation of environmental impacts as their infrastructure ages. Here, we test whether accounting for road repair needs could offer opportunities to boost conservation efficiency by piggybacking connectivity restoration projects on infrastructure maintenance. Using optimization models to align fish passage restoration sites with likely road repair priorities, we find potential increases in conservation return-on-investment ranging from 17% to 25%. Importantly, these gains occur without compromising infrastructure or conservation priorities; simply communicating openly about objectives and candidate sites enables greater accomplishment at current funding levels. Society embraces both reliable roads and thriving fisheries, so overcoming this coordination challenge should be feasible. Given deferred maintenance crises for many types of infrastructure, there could be widespread opportunities to enhance the cost effectiveness of conservation investments by coordinating with infrastructure renewal efforts.


Subject(s)
Built Environment/economics , Ecosystem , Environmental Restoration and Remediation/economics , Fishes , Rivers , Animals , Built Environment/statistics & numerical data , Michigan
5.
Conserv Biol ; 32(4): 894-904, 2018 08.
Article in English | MEDLINE | ID: mdl-29813172

ABSTRACT

Controlling invasive species is critical for conservation but can have unintended consequences for native species and divert resources away from other efforts. This dilemma occurs on a grand scale in the North American Great Lakes, where dams and culverts block tributary access to habitat of desirable fish species and are a lynchpin of long-standing efforts to limit ecological damage inflicted by the invasive, parasitic sea lamprey (Petromyzon marinus). Habitat restoration and sea-lamprey control create conflicting goals for managing aging infrastructure. We used optimization to minimize opportunity costs of habitat gains for 37 desirable migratory fishes that arose from restricting sea lamprey access (0-25% increase) when selecting barriers for removal under a limited budget (US$1-105 million). Imposing limits on sea lamprey habitat reduced gains in tributary access for desirable species by 15-50% relative to an unconstrained scenario. Additional investment to offset the effect of limiting sea-lamprey access resulted in high opportunity costs for 30 of 37 species (e.g., an additional US$20-80 million for lake sturgeon [Acipenser fulvescens]) and often required ≥5% increase in sea-lamprey access to identify barrier-removal solutions adhering to the budget and limiting access. Narrowly distributed species exhibited the highest opportunity costs but benefited more at less cost when small increases in sea-lamprey access were allowed. Our results illustrate the value of optimization in limiting opportunity costs when balancing invasion control against restoration benefits for diverse desirable species. Such trade-off analyses are essential to the restoration of connectivity within fragmented rivers without unleashing invaders.


Subject(s)
Introduced Species , Petromyzon , Animals , Conservation of Natural Resources , Fishes , Lakes
6.
Proc Natl Acad Sci U S A ; 112(19): 6236-41, 2015 May 12.
Article in English | MEDLINE | ID: mdl-25918378

ABSTRACT

In many large ecosystems, conservation projects are selected by a diverse set of actors operating independently at spatial scales ranging from local to international. Although small-scale decision making can leverage local expert knowledge, it also may be an inefficient means of achieving large-scale objectives if piecemeal efforts are poorly coordinated. Here, we assess the value of coordinating efforts in both space and time to maximize the restoration of aquatic ecosystem connectivity. Habitat fragmentation is a leading driver of declining biodiversity and ecosystem services in rivers worldwide, and we simultaneously evaluate optimal barrier removal strategies for 661 tributary rivers of the Laurentian Great Lakes, which are fragmented by at least 6,692 dams and 232,068 road crossings. We find that coordinating barrier removals across the entire basin is nine times more efficient at reconnecting fish to headwater breeding grounds than optimizing independently for each watershed. Similarly, a one-time pulse of restoration investment is up to 10 times more efficient than annual allocations totaling the same amount. Despite widespread emphasis on dams as key barriers in river networks, improving road culvert passability is also essential for efficiently restoring connectivity to the Great Lakes. Our results highlight the dramatic economic and ecological advantages of coordinating efforts in both space and time during restoration of large ecosystems.


Subject(s)
Conservation of Natural Resources/economics , Conservation of Natural Resources/methods , Ecosystem , Animals , Biodiversity , Fishes , Fresh Water , Lakes , Models, Theoretical , Rivers , Spatio-Temporal Analysis , United States , Water Movements
7.
J Pediatr ; 191: 170-178.e2, 2017 12.
Article in English | MEDLINE | ID: mdl-28969890

ABSTRACT

OBJECTIVE: To assess the safety of probiotic Lactobacillus reuteri strain Deutsche Sammlung von Mikroorganismen (DSM) 17938 with daily administration to healthy infants with colic and to determine the effect of L reuteri strain DSM 17938 on crying, fussing, inflammatory, immune, and microbiome variables. STUDY DESIGN: We performed a controlled, double-blinded, phase 1 safety and tolerability trial in healthy breast-fed infants with colic, aged 3 weeks to 3 months, randomly assigned to L reuteri strain DSM 17938 (5 × 108 colony-forming units daily) or placebo for 42 days and followed for 134 days. RESULTS: Of 117 screened infants, 20 were randomized to L reuteri strain DSM 17938 or placebo (sunflower oil) (in a 2:1 ratio) with 80% retention. Eleven of the 20 (55%) presented with low absolute neutrophil counts (<1500/mm3), which resolved in all subjects by day 176. L reuteri strain DSM 17938 produced no severe adverse events and did not significantly change crying time, plasma bicarbonate, or inflammatory biomarkers. Fecal calprotectin decreased rapidly in both groups. In the infants with dominant fecal gram negatives (Klebsiella, Proteus, and Veillonella), resolution of colic was associated with marked decreases in these organisms. CONCLUSIONS: Daily administration of L reuteri strain DSM 17938 appears to be safe in newborn infants with colic, including those with neutropenia, which frequently coexists. A placebo response of 66% suggests that many infants with colic will have resolution within 3 weeks. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01849991.


Subject(s)
Colic/therapy , Limosilactobacillus reuteri , Probiotics/therapeutic use , Biomarkers/metabolism , Colic/diagnosis , Colic/metabolism , Double-Blind Method , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Treatment Outcome
8.
Sex Transm Infect ; 92(6): 441-6, 2016 09.
Article in English | MEDLINE | ID: mdl-26825087

ABSTRACT

OBJECTIVES: As pelvic inflammatory disease (PID) aetiology is not completely understood, we examined the relationship between select novel bacteria, PID and long-term sequelae. METHODS: Fastidious bacterial vaginosis (BV)-associated bacteria (Sneathia (Leptotrichia) sanguinegens, Sneathia amnionii, Atopobium vaginae and BV-associated bacteria 1 (BVAB1)), as well as Ureaplasma urealyticum and Ureaplasma parvum were identified in cervical and endometrial specimens using organism-specific PCR assays among 545 women enrolled in the PID Evaluation and Clinical Health study. Risk ratios and 95% CIs were constructed to determine associations between bacteria, histologically confirmed endometritis, recurrent PID and infertility, adjusting for age, race, gonorrhoea and chlamydia. Infertility models were additionally adjusted for baseline infertility. RESULTS: Persistent detection of BV-associated bacteria was common (range 58% for A. vaginae to 82% for BVAB1) and elevated the risk for persistent endometritis (RRadj 8.5, 95% CI 1.6 to 44.6) 30 days post-cefoxitin/doxycycline treatment, independent of gonorrhoea and chlamydia. In models adjusted for gonorrhoea and chlamydia, endometrial BV-associated bacteria were associated with recurrent PID (RRadj 4.7, 95% CI 1.7 to 12.8), and women who tested positive in the cervix and/or endometrium were more likely to develop infertility (RRadj 3.4, 95% CI 1.1 to 10.4). Associations between ureaplasmas and PID sequelae were modest. CONCLUSIONS: To our knowledge, this is the first prospective study to demonstrate that S. sanguinegens, S. amnionii, BVAB1 and A. vaginae are associated with PID, failure of the Centers for Disease Control and Prevention-recommended treatment to eliminate short-term endometritis, recurrent PID and infertility. Optimal antibiotic regimens for PID may require coverage of novel BV-associated microbes.


Subject(s)
Endometritis/microbiology , Infertility, Female/microbiology , Pelvic Inflammatory Disease/microbiology , Vagina/microbiology , Vaginosis, Bacterial/microbiology , Adolescent , Adult , Anti-Bacterial Agents/therapeutic use , Cefoxitin/therapeutic use , Doxycycline/therapeutic use , Drug Therapy, Combination , Endometritis/drug therapy , Endometritis/epidemiology , Female , Humans , Infertility, Female/prevention & control , Pelvic Inflammatory Disease/drug therapy , Pelvic Inflammatory Disease/epidemiology , Prospective Studies , United States/epidemiology , Vaginosis, Bacterial/drug therapy , Vaginosis, Bacterial/epidemiology , Young Adult
9.
PLoS Comput Biol ; 10(5): e1003626, 2014 May.
Article in English | MEDLINE | ID: mdl-24874113

ABSTRACT

Systematic, genome-wide loss-of-function experiments can be used to identify host factors that directly or indirectly facilitate or inhibit the replication of a virus in a host cell. We present an approach that combines an integer linear program and a diffusion kernel method to infer the pathways through which those host factors modulate viral replication. The inputs to the method are a set of viral phenotypes observed in single-host-gene mutants and a background network consisting of a variety of host intracellular interactions. The output is an ensemble of subnetworks that provides a consistent explanation for the measured phenotypes, predicts which unassayed host factors modulate the virus, and predicts which host factors are the most direct interfaces with the virus. We infer host-virus interaction subnetworks using data from experiments screening the yeast genome for genes modulating the replication of two RNA viruses. Because a gold-standard network is unavailable, we assess the predicted subnetworks using both computational and qualitative analyses. We conduct a cross-validation experiment in which we predict whether held-aside test genes have an effect on viral replication. Our approach is able to make high-confidence predictions more accurately than several baselines, and about as well as the best baseline, which does not infer mechanistic pathways. We also examine two kinds of predictions made by our method: which host factors are nearest to a direct interaction with a viral component, and which unassayed host genes are likely to be involved in viral replication. Multiple predictions are supported by recent independent experimental data, or are components or functional partners of confirmed relevant complexes or pathways. Integer program code, background network data, and inferred host-virus subnetworks are available at http://www.biostat.wisc.edu/~craven/chasman_host_virus/.


Subject(s)
Cell Transformation, Viral/physiology , Fungal Proteins/metabolism , RNA Viruses/physiology , Signal Transduction/physiology , Virus Replication/physiology , Yeasts/metabolism , Yeasts/virology , Gene Expression Regulation, Fungal/physiology , Genes, Viral
10.
J Infect Dis ; 207(12): 1922-31, 2013 Jun 15.
Article in English | MEDLINE | ID: mdl-23482642

ABSTRACT

BACKGROUND: The prevalence of Trichomonas vaginalis infection is highest in women with intermediate Nugent scores. We hypothesized that the vaginal microbiota in T. vaginalis-infected women differs from that in T. vaginalis-uninfected women. METHODS: Vaginal samples from 30 T. vaginalis-infected women were matched by Nugent score to those from 30 T. vaginalis-uninfected women. Equal numbers of women with Nugent scores categorized as normal, intermediate, and bacterial vaginosis were included. The vaginal microbiota was assessed using 454 pyrosequencing analysis of polymerase chain reaction-amplified 16S ribosomal RNA gene sequences. The 16S ribosomal RNA gene sequence of an unknown organism was obtained by universal bacterial polymerase chain reaction amplification, cloning, and sequencing. RESULTS: Principal coordinates analysis of the pyrosequencing data showed divergence of the vaginal microbiota in T. vaginalis-infected and T. vaginalis-uninfected patients among women with normal and those with intermediate Nugent scores but not among women with bacterial vaginosis. Cluster analysis revealed 2 unique groups of T. vaginalis-infected women. One had high abundance of Mycoplasma hominis and other had high abundance of an unknown Mycoplasma species. Women in the former group had clinical evidence of enhanced vaginal inflammation. CONCLUSIONS: T. vaginalis may alter the vaginal microbiota in a manner that is favorable to its survival and/or transmissibility. An unknown Mycoplasma species plays a role in some of these transformations. In other cases, these changes may result in a heightened host inflammatory response.


Subject(s)
Mycoplasma/classification , Trichomonas Vaginitis/microbiology , Trichomonas vaginalis/isolation & purification , Vagina/microbiology , Vaginosis, Bacterial/microbiology , Adult , Base Sequence , Cluster Analysis , Cohort Studies , Cross-Sectional Studies , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Demography , Female , High-Throughput Nucleotide Sequencing , Humans , Metagenome/genetics , Molecular Sequence Data , Mycoplasma/genetics , Mycoplasma/isolation & purification , Mycoplasma hominis/genetics , Mycoplasma hominis/isolation & purification , New Orleans/epidemiology , Phylogeny , Prevalence , RNA, Bacterial/genetics , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Trichomonas Vaginitis/complications , Trichomonas Vaginitis/epidemiology , Trichomonas vaginalis/genetics , Vaginosis, Bacterial/complications , Vaginosis, Bacterial/epidemiology
11.
Appl Environ Microbiol ; 79(8): 2648-56, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23396345

ABSTRACT

Mycobacterium ulcerans is an emerging environmental pathogen that causes debilitating, ulcerative disease in humans and other vertebrates. The majority of human cases occur in tropical and temperate regions of Africa and Australia, and outbreaks of piscine mycobacteriosis caused by M. ulcerans have been reported in disparate geographic locations spanning the globe. While exposure to a natural body of water is the most common risk factor for human infection, the environmental distribution of M. ulcerans in aquatic habitats has not been extensively studied. Although no human cases have been reported in the United States, a strain of M. ulcerans has been identified as the cause of a piscine mycobacteriosis in Striped bass (Morone saxatilis) within the Chesapeake Bay. Infected fish exhibit bright red ventral and lateral dermal lesions. We observed a possible outbreak causing similar lesions on red drum (Sciaenops ocellatus) in wetlands of southern Louisiana and detected M. ulcerans-specific genetic markers in lesion samples from these fish. Based on these findings, we studied the geographic and seasonal prevalence of these markers across southern Louisiana. M. ulcerans was detected in each of the nine areas sampled across the state. M. ulcerans prevalence was significantly lower in the fall samples, and the low prevalence coincided with decreased nutrient levels and an increase in water temperature. To our knowledge, this is the first study of M. ulcerans biomarkers in the southern United States.


Subject(s)
Lakes/microbiology , Mycobacterium ulcerans/genetics , Mycobacterium ulcerans/isolation & purification , Water Microbiology , Aquatic Organisms/microbiology , Bacterial Proteins/genetics , Bacterial Proteins/isolation & purification , Base Sequence , Biofilms , Biomarkers , Geography , Louisiana , Mycobacterium ulcerans/growth & development , Phylogeny , Seasons , Sequence Analysis, DNA
12.
J Pediatr Gastroenterol Nutr ; 56(4): 397-400, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23254444

ABSTRACT

OBJECTIVES: Bacterial colonization is considered a major risk factor for necrotizing enterocolitis (NEC). The objective of the present study was to test the hypothesis that histamine-2 receptor (H2-) blockers alter colonic bacterial colonization by analyzing and comparing the fecal microbiota in premature infants with and without H2-blocker therapy using sensitive molecular biological techniques. METHODS: Seventy-six premature infants ≤1500 g or <34 weeks gestation were enrolled in this case-controlled, cross-sectional study. Stool samples were collected from 25 infants receiving H2-blockers and 51 babies who had never received them. Following DNA extraction and PCR amplification of 16S rRNA, 454 pyrosequencing was undertaken and the resulting sequences were subjected to comparison with published sequence libraries. RESULTS: Proteobacteria and Firmicutes were the major phyla contributing to fecal microbial communities. Microbial diversity was lower, relative abundance of Proteobacteria (primarily of the family Enterobacteriaceae) was increased, whereas that of Firmicutes was decreased in the stools of infants receiving H2-blockers compared with those who had never received them. CONCLUSIONS: Although not designed to look specifically at the effect of H2-blockers on the incidence of NEC, our study suggests that their use lowers fecal microbial diversity and shifts the microfloral pattern toward Proteobacteria. These alterations in fecal microbiota may predispose the vulnerable immature gut to necrotizing enterocolitis and suggest prudence in the use of H2-blockers in the premature infant.


Subject(s)
Feces/microbiology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Histamine H2 Antagonists/therapeutic use , Intestinal Mucosa/drug effects , Intestines/drug effects , Case-Control Studies , Child Development , Cross-Sectional Studies , Enterocolitis, Necrotizing/epidemiology , Enterocolitis, Necrotizing/microbiology , Enterocolitis, Necrotizing/prevention & control , Female , Gram-Negative Bacteria/growth & development , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/growth & development , Gram-Positive Bacteria/isolation & purification , Histamine H2 Antagonists/adverse effects , Humans , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/epidemiology , Infant, Premature, Diseases/microbiology , Infant, Premature, Diseases/prevention & control , Intestinal Mucosa/growth & development , Intestinal Mucosa/microbiology , Intestines/growth & development , Intestines/microbiology , Longitudinal Studies , Louisiana/epidemiology , Male , Proteobacteria/drug effects , Proteobacteria/growth & development , Proteobacteria/isolation & purification , Risk Factors
13.
Trans Am Clin Climatol Assoc ; 123: 242-56, 2012.
Article in English | MEDLINE | ID: mdl-23303991

ABSTRACT

Based on traditional microbiological methods, namely cultivation and microscopic analyses, the vaginal microbiota (VMB) has been defined as healthy when it is predominated by hydrogen peroxide-producing Lactobacillus spp., most prominently Lactobacillis crispatus. Similarly, the VMB has been defined as bacterial vaginosis (BV) when it is predominated by Gardnerella vaginalis as well as a number of other anaerobic bacterial species. BV is associated with a distinct vaginal discharge syndrome, poor pregnancy outcomes, pelvic inflammatory disease, post-operative wound infections, and endometritis after elective abortions. Additionally, BV predisposes women to infection by HIV as well as other sexually transmitted diseases (STDs). The application of molecular techniques over the last decade to studies of the VMB has significantly advanced our understanding of its structure and variation. It is now clear that the diversity of the VMB is far more complex than previously recognized; it is comprised of many heretofore unknown bacteria in addition to those previously identified by culture. Here we describe the application of 454 pyrosequencing technology to a study of vaginal specimens from 92 women attending the New Orleans STD clinic in an effort to obtain a more precise view of how different types of "trees" (bacteria) assemble to form a recognizable "forest" (VMB). This knowledge will be useful in the design of future clinical studies that investigate the mechanisms by which the vaginal microbiome influences human health and disease.


Subject(s)
Metagenome , Urogenital System/microbiology , Vagina/microbiology , Escherichia coli/isolation & purification , Female , Humans , Lactobacillus/isolation & purification , New Orleans , Retrospective Studies , Shigella/isolation & purification
14.
Article in English | MEDLINE | ID: mdl-34199071

ABSTRACT

Clam Beach is located in Northern California, USA, and is listed as an impaired waterway by the federal government. The scope of this study was to investigate this beach and surrounding watershed to determine, if possible, the source of the impairment by conducting an 11-h beach study and 8-week watershed study. We used traditional fecal indicator bacteria (FIB) and microbial source tracking (MST) methods to help identify source(s) of the FIB. Our study was focused on four possible contributors: human, ruminant, canine, and bird. A total of 169 samples were collected, analyzed, and compared to the California Department of Health single sample maximum (SSM) objective. In the beach study, 29 (44%) samples exceeded at least one SSM objective, which would have resulted in a resample per state regulations for recreational primary contact use. MST methods showed that the most abundant marker detected was bird, in 65% of the samples, but varied by sample location, which is likely due to a natural population of nearshore birds regularly observed along Clam Beach. The watershed study highlighted the potential influence from ruminants throughout the region, while humans did not appear to be a significant contributor. Health risk to humans appears to be low.


Subject(s)
Bivalvia , Animals , Bathing Beaches , California , Dogs , Environmental Monitoring , Feces , Humans , Water Microbiology
15.
J Nucl Med ; 2021 Mar 19.
Article in English | MEDLINE | ID: mdl-33741648

ABSTRACT

Objectives: To assess the safety and clinical impact of a novel, kit-based formulation of 68Ga-THP PSMA positron emission tomography/computed tomography (PET/CT) when used to guide the management of patients with prostate cancer (PCa). Methods: Patients were prospectively recruited in to one of: Group A: high-risk untreated prostate cancer; Gleason score >4+3, or PSA >20 ng/mL or clinical stage >T2c. Group B: biochemical recurrence (BCR) and eligible for salvage treatment after radical prostatectomy with two consecutive rises in prostate specific antigen (PSA) with a three month interval in between reads and final PSA >0.1 ng/mL or a PSA level >0.5 ng/mL. Group C: BCR with radical curative radiotherapy or brachytherapy at least three months prior to enrolment, and an increase in PSA level >2.0 ng/mL above the nadir level after radiotherapy or brachytherapy. Patients underwent evaluation with PET/CT 60 minutes following intravenous administration of 160±30 MBq of 68Ga-THP PSMA. Safety was assessed by means including vital signs, cardiovascular profile, serum haematology, biochemistry, urinalysis, PSA, and Adverse Events (AEs). A change in management was reported when the predefined clinical management of the patient altered as a result of 68Ga-THP PSMA PET/CT findings. Results: Forty-nine patients were evaluated with PET/CT; 20 in Group A, 21 in Group B and 8 in Group C. No patients experienced serious AEs discontinued the study due to AEs, or died during the study. Two patients had Treatment Emergent AEs attributed to 68Ga-THP-PSMA (pruritus in one patient and intravenous catheter site rash in another). Management change secondary to PET/CT occurred in 42.9% of all patients; 30% in Group A, 42.9% in Group B and 75% in Group C. Conclusion: 68Ga-THP PSMA was safe to use with no serious AE and no AE resulting in withdrawal from the study. 68Ga-THP PSMA PET/CT changed the management of patients in 42.9% of the study population, comparable to studies using other PSMA tracers. These data form the basis of a planned Phase III study of 68Ga-THP PSMA in patients with prostate cancer.

16.
J Clin Microbiol ; 48(5): 1812-9, 2010 May.
Article in English | MEDLINE | ID: mdl-20305015

ABSTRACT

Knowledge of the abundance of bacterial species in vaginal communities will help us to better understand their role in health and disease. However, progress in this field has been limited because quantifying bacteria in natural specimens is an arduous process. We developed quantitative real-time PCR (qPCR) assays to facilitate assessments of bacterial abundance in vaginal specimens and evaluated the utility of these assays by measuring species abundance in patients whose vaginal floras were clinically described as normal, intermediate, or bacterial vaginosis (BV) as defined by Nugent's criteria. The qPCR measurements showed that Lactobacillus species were predominant in normal vaginal specimens and that high Lactobacillus crispatus and Lactobacillus jensenii abundance was specific to normal specimens, while Lactobacillus iners abundance was high in all categories including BV. The abundances of all non-Lactobacillus species were higher in BV specimens than in normal specimens. Prevotella species were prevalent in all specimens and represented a high percentage of total species in BV specimens. qPCR assays can be a useful tool for describing the structure of vaginal communities and elucidating their role in health and disease.


Subject(s)
Bacteria/isolation & purification , Bacteriological Techniques/methods , Metagenome , Polymerase Chain Reaction/methods , Vagina/microbiology , Vaginosis, Bacterial/microbiology , Adult , Bacteria/classification , Bacteria/genetics , Colony Count, Microbial , Female , Humans
17.
J Pediatr ; 155(6): 823-828.e1, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19628216

ABSTRACT

OBJECTIVE: We explored whether gut inflammation, colonic fermentation, and/or an altered colonic flora could provide a pathophysiological mechanism for colic. STUDY DESIGN: The study population consisted of 36 term infants ranging in age from 14 to 81 days. We measured fecal calprotectin (a marker of neutrophil infiltration) by ELISA; stool microorganisms by denaturing gradient gel electrophoresis, cloning, and sequencing; and breath hydrogen levels using gas chromatography. RESULTS: During 24 hours, infants with colic (n = 19) cried and fussed for a mean of 314 +/- 36 (SEM) minutes, compared with control infants (n = 17, 103 +/- 17 minutes). Fecal calprotectin levels were 2-fold higher in infants with colic than in control infants (413 +/- 71 vs 197 +/- 46 microg/g, P = .042). Stools of infants with colic had fewer identifiable bands on denaturing gradient gel electrophoresis. Klebsiella species were detected in more colic patients than in control patients (8 vs 1, P = .02), whereas Enterobacter/Pantoea species were detected only in the control patients. These differences could not be attributed to differences in formula versus breast milk feeding, consumption of elemental formula, or exposure to antibiotics. CONCLUSIONS: Infants with colic, a condition previously believed to be nonorganic in nature, have evidence of intestinal neutrophilic infiltration and a less diverse fecal microflora.


Subject(s)
Colic/metabolism , Colic/microbiology , Feces/chemistry , Feces/microbiology , Leukocyte L1 Antigen Complex/metabolism , Breath Tests , Case-Control Studies , Colic/pathology , Crying , Female , Gastroenteritis/complications , Gastroenteritis/metabolism , Gastroenteritis/microbiology , Humans , Hydrogen/metabolism , Infant , Infant, Newborn , Leukocyte L1 Antigen Complex/analysis , Male , Neutrophil Infiltration/physiology
18.
Stem Cell Reports ; 12(6): 1269-1281, 2019 06 11.
Article in English | MEDLINE | ID: mdl-31080110

ABSTRACT

Contractile to synthetic phenotypic switching of smooth muscle cells (SMCs) contributes to stenosis in vascular disease and vascular transplants. To generate more contractile SMCs, we performed a high-throughput differentiation screen using a MYH11-NLuc-tdTomato human embryonic stem cell reporter cell line. We identified RepSox as a factor that promotes differentiation of MYH11-positive cells by promoting NOTCH signaling. RepSox induces SMCs to exhibit a more contractile phenotype than SMCs generated using PDGF-BB and TGF-ß1, two factors previously used for SMC differentiation but which also cause intimal hyperplasia. In addition, RepSox inhibited intimal hyperplasia caused by contractile to synthetic phenotypic switching of SMCs in a rat balloon injury model. Thus, in addition to providing more contractile SMCs that could prove useful for constructing artificial blood vessels, this study suggests a strategy for identifying drugs for inhibiting intimal hyperplasia that act by driving contractile differentiation rather than inhibiting proliferation non-specifically.


Subject(s)
Cell Differentiation , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Pluripotent Stem Cells/metabolism , Tunica Intima/metabolism , Animals , Becaplermin/metabolism , Disease Models, Animal , Humans , Hyperplasia , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/pathology , Myosin Heavy Chains/metabolism , Pluripotent Stem Cells/pathology , Rats , Transforming Growth Factor beta1/metabolism , Tunica Intima/pathology
19.
Appl Environ Microbiol ; 74(5): 1656-9, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18203860

ABSTRACT

Cultivation-independent analysis of 16S rRNA gene sequences in vaginal samples revealed two previously unrecognized, uncultivated Megasphaera-like phylotypes. Phylogenetic analysis and environmental distribution suggest that these Megasphaera types may be unique to the vaginal environment. Quantitative PCR suggests that both phylotypes are present in higher concentrations in women with bacterial vaginosis.


Subject(s)
Megasphaera/genetics , Phylogeny , Vagina/microbiology , Vaginosis, Bacterial/epidemiology , Vaginosis, Bacterial/microbiology , Base Sequence , Cluster Analysis , DNA Primers/genetics , Female , Humans , Louisiana/epidemiology , Megasphaera/classification , Molecular Sequence Data , Prevalence , RNA, Ribosomal, 16S/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Species Specificity
20.
Phys Med Biol ; 53(4): 1057-69, 2008 Feb 21.
Article in English | MEDLINE | ID: mdl-18263958

ABSTRACT

We describe the application of a Bayesian variable-number sample-path (VNSP) optimization algorithm to yield a robust design for a floating sleeve antenna for hepatic microwave ablation. Finite element models are used to generate the electromagnetic (EM) field and thermal distribution in liver given a particular design. Dielectric properties of the tissue are assumed to vary within +/- 10% of average properties to simulate the variation among individuals. The Bayesian VNSP algorithm yields an optimal design that is a 14.3% improvement over the original design and is more robust in terms of lesion size, shape and efficiency. Moreover, the Bayesian VNSP algorithm finds an optimal solution saving 68.2% simulation of the evaluations compared to the standard sample-path optimization method.


Subject(s)
Catheter Ablation/instrumentation , Liver Neoplasms/surgery , Microwaves/therapeutic use , Algorithms , Bayes Theorem , Models, Biological
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