Decision support for nitrogen management in tile-drained agriculture

Farmers will adopt alternative management systems to improve water quality more readily if they understand how those management alternatives affect the release of contaminants, crop yields, and ultimately, their net income. We propose a method to address these issues by integrating observed data from field experiments, a comprehensive simulation model, review by local experts, and application through a decision support system by technically trained conservationists. An example for reducing nitrogen loading from tile-drained corn and soybean production in Iowa demonstrates the approach. Fourteen years of observed data from 30 research plots on the Northeast Research and Demonstration Farm near Nashua, Iowa were used to calibrate the Root Zone Water Quality Model (RZWQM) to simulate the effects of 35 management systems on crop yields and nitrogen (N) loadings into tile drains. The EconDocs tool was used for an economic analysis of the management effects. An Expert Panel reviews the simulations and the long term average annual management effects. Those management effects, as well as the daily values of variables that describe the crop growth and nitrogen loading in tile flow processes, are put into a database. As part of the conservation planning process, Conservationists and farmers would use the database inside a decision support system to select management systems that meet the farmers\u27 goals and reduce water quality problems

Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis

The discovery of novel antigens is an essential requirement in devising new diagnostics or vaccines for use in control programmes against human tuberculosis (TB) and bovine tuberculosis (bTB). Identification of potential epitopes recognised by CD4+ T cells requires prediction of peptide binding to MHC class-II, an obligatory prerequisite for T cell recognition. To comprehensively prioritise potential MHC-II-binding epitopes from Mycobacterium bovis, the agent of bTB and zoonotic TB in humans, we integrated three binding prediction methods with the M. bovisproteome using a subset of human HLA alleles to approximate the binding of epitope-containing peptides to the bovine MHC class II molecule BoLA-DRB3. Two parallel strategies were then applied to filter the resulting set of binders: identification of the top-scoring binders or clusters of binders. Our approach was tested experimentally by assessing the capacity of predicted promiscuous peptides to drive interferon-γ secretion from T cells of M. bovis infected cattle. Thus, 376 20-mer peptides, were synthesised (270 predicted epitopes, 94 random peptides with low predictive scores and 12 positive controls of known epitopes). The results of this validation demonstrated significant enrichment (>24 %) of promiscuously recognised peptides predicted in our selection strategies, compared with randomly selected peptides with low prediction scores. Our strategy offers a general approach to the identification of promiscuous epitopes tailored to target populations where there is limited knowledge of MHC allelic diversity

Aduhelm, a novel anti-amyloid monoclonal antibody, for the treatment of Alzheimer\u27s Disease: A comprehensive review.

Alzheimer\u27s disease (AD) is the most common form of dementia affecting millions of individuals, including family members who often take on the role of caregivers. This debilitating disease reportedly consumes 8% of the total United States healthcare expenditure, with medical and nursing outlays accounting for an estimated $290 billion. Cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists have historically been the most widely used pharmacologic therapies for patients with AD; however, these drugs are not curative. The present investigation describes the epidemiology, pathophysiology, risk factors, presentation, and current treatment of AD followed by the role of the novel monoclonal antibody, Adulhelm, in the treatment of AD. Currently, Adulhelm is the only Food and Drug Administration (FDA) approved drug that acts to slow the progression of this disease. Adulhelm is an anti-amyloid drug that functions by selectively binding amyloid aggregates in both the oligomeric and fibrillar states. Studies show Adulhelm may help to restore neurological function in patients with AD by reducing beta-amyloid plaques and reestablishing neuronal calcium permeability. At present, there is concern the magnitude of this drug\u27s benefit may only be statistically significant, although not clinically significant. Despite skepticism, Adulhelm has proven to significantly decrease amyloid in all cortical brain regions examined. With such high stakes and potential, further research into Adulhelm\u27s clinical efficacy is warranted in the treatment of AD

International Society for Pharmacoeconomics and Outcomes Research Comments on the American Society of Clinical Oncology Value Framework

As members of the International Society for Pharmacoeconomics and Outcomes Research, we read with great interest the new American Society of Clinical Oncology (ASCO) conceptual framework to assess the value of cancer treatment options.1 We applaud the Value in Cancer Care Task Force for proposing a conceptual framework to support clinicians and patients in assessing the value of new cancer treatments. We acknowledge the challenges facing clinician–patient decision making, particularly concerning cancer treatments. Like ASCO, we recognize that the cost of treatments is increasingly being placed on patients through cost sharing and that engaging patients as part of making individual treatment decisions is of high importance. The ASCO framework highlights the growing tension among patients, insurance companies, and product manufacturers in a dynamic health care environment. In that light, the framework deserves a field test, and we look forward to seeing the outcome of that experience. We also appreciate the opportunity to offer comments and suggestions on the ASCO framework at this early stage, and our membership stands ready to support ASCO in future enhancements

Transformation of RDX and other energetic compounds by xenobiotic reductases XenA and XenB

The transformation of explosives, including hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), by xenobiotic reductases XenA and XenB (and the bacterial strains harboring these enzymes) under both aerobic and anaerobic conditions was assessed. Under anaerobic conditions, Pseudomonas fluorescens I-C (XenB) degraded RDX faster than Pseudomonas putida II-B (XenA), and transformation occurred when the cells were supplied with sources of both carbon (succinate) and nitrogen (NH\u2084\u207a), but not when only carbon was supplied. Transformation was always faster under anaerobic conditions compared to aerobic conditions, with both enzymes exhibiting a O\u2082 concentration-dependent inhibition of RDX transformation. The primary degradation pathway for RDX was conversion to methylenedinitramine and then to formaldehyde, but a minor pathway that produced 4-nitro-2,4-diazabutanal (NDAB) also appeared to be active during transformation by whole cells of P. putida II-B and purified XenA. Both XenA and XenB also degraded the related nitramine explosives octahydro- 1,3,5,7-tetranitro-1,3,5,7-tetrazocine and 2,4,6,8,10,12- hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane. Purified XenB was found to have a broader substrate range than XenA, degrading more of the explosive compounds examined in this study. The results show that these two xenobiotic reductases (and their respective bacterial strains) have the capacity to transform RDX as well as a wide variety of explosive compounds, especially under low oxygen concentrations.NRC publication: Ye

Experimental infection of cattle with Mycobacterium tuberculosis isolates shows the attenuation of the human tubercle bacillus for cattle

The Mycobacterium tuberculosis complex (MTBC) is the collective term given to the group of bacteria that cause tuberculosis (TB) in mammals. It has been reported that M. tuberculosis H37Rv, a standard reference MTBC strain, is attenuated in cattle compared to Mycobacterium bovis. However, as M. tuberculosis H37Rv was isolated in the early 1930s, and genetic variants are known to exist, we sought to revisit this question of attenuation of M. tuberculosis for cattle by performing a bovine experimental infection with a recent M. tuberculosis isolate. Here we report infection of cattle using M. bovis AF2122/97, M. tuberculosis H37Rv, and M. tuberculosis BTB1558, the latter isolated in 2008 during a TB surveillance project in Ethiopian cattle. We show that both M. tuberculosis strains caused reduced gross and histopathology in cattle compared to M. bovis. Using M. tuberculosis H37Rv and M. bovis AF2122/97 as the extremes in terms of infection outcome, we used RNA-Seq analysis to explore differences in the peripheral response to infection as a route to identify biomarkers of progressive disease in contrast to a more quiescent, latent infection. Our work shows the attenuation of M. tuberculosis strains for cattle, and emphasizes the potential of the bovine model as a ‘One Health’ approach to inform human TB biomarker development and post-exposure vaccine development

Aduhelm, a novel anti-amyloid monoclonal antibody, for the treatment of Alzheimer’s Disease: A comprehensive review

Alzheimer's disease (AD) is the most common form of dementia affecting millions of individuals, including family members who often take on the role of caregivers. This debilitating disease reportedly consumes 8% of the total United States healthcare expenditure, with medical and nursing outlays accounting for an estimated \$290 billion. Cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists have historically been the most widely used pharmacologic therapies for patients with AD; however, these drugs are not curative. The present investigation describes the epidemiology, pathophysiology, risk factors, presentation, and current treatment of AD followed by the role of the novel monoclonal antibody, Adulhelm, in the treatment of AD. Currently, Adulhelm is the only Food and Drug Administration (FDA) approved drug that acts to slow the progression of this disease. Adulhelm is an anti-amyloid drug that functions by selectively binding amyloid aggregates in both the oligomeric and fibrillar states. Studies show Adulhelm may help to restore neurological function in patients with AD by reducing beta-amyloid plaques and reestablishing neuronal calcium permeability. At present, there is concern the magnitude of this drug's benefit may only be statistically significant, although not clinically significant. Despite skepticism, Adulhelm has proven to significantly decrease amyloid in all cortical brain regions examined. With such high stakes and potential, further research into Adulhelm's clinical efficacy is warranted in the treatment of AD

Photonic Doppler velocimetry probe used to measure grain boundaries of dynamic shocked materials

Author Institution: Mission Support and Test Services, LLC; Los Alamos National LaboratorySlides presented at the 2018 Photonic Doppler Velocimetry (PDV) Users Workshop, Drury Plaza Hotel, Santa Fe, New Mexico, May 16-18, 2018

Simultaneous quantification of 12 different nucleotides and nucleosides released from renal epithelium and in human urine samples using ion-pair reversed-phase HPLC

Nucleotides and nucleosides are not only involved in cellular metabolism but also act extracellularly via P1 and P2 receptors, to elicit a wide variety of physiological and pathophysiological responses through paracrine and autocrine signalling pathways. For the first time, we have used an ion-pair reversed-phase high-performance liquid chromatography ultraviolet (UV)-coupled method to rapidly and simultaneously quantify 12 different nucleotides and nucleosides (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, adenosine, uridine triphosphate, uridine diphosphate, uridine monophosphate, uridine, guanosine triphosphate, guanosine diphosphate, guanosine monophosphate, guanosine): (1) released from a mouse renal cell line (M1 cortical collecting duct) and (2) in human biological samples (i.e., urine). To facilitate analysis of urine samples, a solid-phase extraction step was incorporated (overall recovery rate ? 98 %). All samples were analyzed following injection (100 ?l) into a Synergi Polar-RP 80 Å (250 × 4.6 mm) reversed-phase column with a particle size of 10 ?m, protected with a guard column. A gradient elution profile was run with a mobile phase (phosphate buffer plus ion-pairing agent tetrabutylammonium hydrogen sulfate; pH 6) in 2-30 % acetonitrile (v/v) for 35 min (including equilibration time) at 1 ml min(-1) flow rate. Eluted compounds were detected by UV absorbance at 254 nm and quantified using standard curves for nucleotide and nucleoside mixtures of known concentration. Following validation (specificity, linearity, limits of detection and quantitation, system precision, accuracy, and intermediate precision parameters), this protocol was successfully and reproducibly used to quantify picomolar to nanomolar concentrations of nucleosides and nucleotides in isotonic and hypotonic cell buffers that transiently bathed M1 cells, and urine samples from normal subjects and overactive bladder patients

Single- and Multiple-Dose Pharmacokinetics of Darunavir Plus Ritonavir and Etravirine in Semen and Rectal Tissue of HIV-Negative Men

Antiretroviral therapy (ART) has become a central component of combination HIV prevention efforts. Defining the individual exposure of commercially available ART in genital secretions and vulnerable mucosal tissues is paramount to designing future prevention interventions