Challenges and Perspectives

Agriculture is a diverse field that produces a wide array of products vital to society. As global populations continue to grow the competition for natural resources will increase pressure on agricultural production of food, fiber, energy, and various high value by-products. With elevated concerns related to environmental impacts associated with the needs of a growing population, a life cycle assessment (LCA) framework can be used to determine areas of greatest impact and compare reduction strategies for agricultural production systems. The LCA methodology was originally developed for industrial operations but has been expanded to a wider range of fields including agriculture. There are various factors that increase the complexity of determining impacts associated with agricultural production including multiple products from a single system, regional and crop specific management techniques, temporal variations (seasonally and annually), spatial variations (multilocation production of end products), and the large quantity of nonpoint emission sources. The lack of consistent methodology of some impacts that are of major concern to agriculture (e.g., land use and water usage) increases the complexity of this analysis. This paper strives to review some of these issues and give perspective to the LCA practitioner in the field of agriculture

Are non-allergic drug reactions commonly documented as medication “allergies”? A national cohort of Veterans\u27 admissions from 2000 to 2014

Purpose: Adverse drug reactions (ADRs) including medication allergies are not well-described among large national cohorts. This study described the most common documented medication allergies and their reactions among a national cohort of Veterans Affairs (VA) inpatients. Methods: We evaluated inpatient admissions in any VA Medical Center from 1 January 2000 to 31 December 2014. Each admission was linked with allergy history preceding or upon admission. Individual drugs were aggregated into drug class category including: penicillins, sulfonamides, angiotensin converting enzyme (ACE) inhibitors, opiates, HMG-CoA reductase inhibitors (“statins”) and non-steroidal anti-inflammatory inhibitors (NSAID). Results were reported in aggregate and over time. Results: Approximately ~10.8 million inpatient admissions occurred from 2000 to 2014. We found the most commonly reported allergy drug classes were penicillins (13%, n = 1 410 080), opiates (9.1%, n = 984 978), ACE inhibitors (5.7%, n = 618 075) sulfonamides (5.1%, n = 558 653), NSAIDs (5.1%, n = 551 216) and statins (3.6%, n  = 391 983). Several allergy histories increased over time including opiates (6.2 to 11.2%), ACE inhibitors (1.3 to 10.2%), statins (0.3 to 7.3%) and NSAIDs (3.9 to 6.0%). Rash was the most commonly documented reaction on reports for penicillins (25.5%, n = 371 825), sulfonamides (25.6%, n = 165 954) and NSAIDs (10.3%, n = 65 741). The most common reaction for opiates was nausea/vomiting (17.9%, n = 211 864), cough/coughing for ACE inhibitors (41.0%, n = 270 537) and muscle pain/myalgia for statins (34.1%, n = 186 565). Conclusions: We report that penicillins and opiates are the most commonly documented drug allergies among VA inpatients, but other drug classes such as ACE inhibitors, statins and NSAIDs are becoming increasingly common. Clinicians also commonly document non-allergic ADRs in the allergy section such as cough or myalgia. Copyright © 2016 John Wiley & Sons, Ltd

The Effect of Molecular Rapid Diagnostic Testing on Clinical Outcomes in Bloodstream Infections: A Systematic Review & Meta-analysis

Background. Previous reports on molecular rapid diagnostic testing (mRDT) do not consistently demonstrate improved clinical outcomes in bloodstream infections (BSIs). This meta-analysis seeks to evaluate the impact of mRDT in improving clinical outcomes in BSIs. Methods. We searched PubMed, CINAHL, Web of science, and EMBASE through May 2016 for BSI studies comparing clinical outcomes by mRDT and conventional microbiology methods. Results. Thirty-one studies were included with 5,920 patients. Risk of morality was significantly lower with mRDT as compared to conventional microbiology methods (OR 0.66, 95% CI 0.54-0.80) yielding a NNT of 20. The risk of mortality was slightly lower with mRDT in studies with antimicrobial stewardship programs (ASPs) (OR 0.64, 95% CI 0.51-0.79) and non-ASP studies failed to demonstrate a significant decrease in risk of mortality (OR 0.72, 95% CI 0.46-1.12). Significant decreases in mortality risk were observed with both Gram-positive (OR 0.73, 95% CI 0.55-0.97) and Gram-negative organisms (OR 0.51, 95% CI 0.33-0.78) but not yeast (OR 0.90, 95% CI 0.49-1.67). Time to effective therapy decreased by a weighted mean difference of -5.03 hours (95% CI -8.60 to -1.45) and length of stay decreased by -2.48 days (95% CI -3.90 to -1.06). Conclusions. For BSIs, mRDT was associated with significant decreases in risk of mortality in the presence of a ASP, but not in its absence. Additionally, mRDT decreased time to effective therapy and length of stay. mRDT should be considered as part of the standard of care in patients with BSIs

Tissue-specific expression of high-voltage-activated dihydropyridine-sensitive L-type calcium channels

The cloning of the cDNA for the α1 subunit of L-type calcium channels revealed that at least two genes (CaCh1 and CaCh2) exist which give rise to several splice variants. The expression of mRNA for these α1 subunits and the skeletal muscle α2/δ, β and γ subunits was studied in rabbit tissues and BC3H1 cells. Nucleic-acid-hybridization studies showed that the mRNA of all subunits are expressed in skeletal muscle, brain, heart and aorta. However, the α1-, β- and γ-specific transcripts had different sizes in these tissues. Smooth muscle and heart contain different splice variants of the CaCh2 gene. The α1, β and γ mRNA are expressed together in differentiated but not in proliferating BC3H1 cells. A probe specific for the skeletal muscle α2/δ subunit did not hybridize to poly(A)-rich RNA from BC3H1 cells. These results suggest that different splice variants of the genes for the α1, β and γ subunits exist in tissues containing L-type calcium channels, and that their expression is regulated in a coordinate manner

Attitudes Towards and Limitations to ICT Use in Assisted and Independent Living Communities: Findings from a Specially-Designed Technological Intervention

Much literature has been devoted to theoretical explanations of the learning processes of older adults and to the methods of teaching best utilized in older populations. However, there has been less focus on the education of older adults who reside in assisted and independent living communities (AICs), especially with regards to information and communication technology (ICT) education. The purpose of this study is to determine whether participants\u27 attitudes and views towards computers and the Internet are affected as a result of participating in an eight-week training program designed to enhance computer and Internet use among older adults in such communities. Specifically, we examine if ICT education specially designed for AIC residents results in more positive attitudes towards ICTs and a perceived decrease in factors that may limit or prevent computer and Internet use. We discuss the implications of these results for enhancing the quality of life for older adults in AICs and make recommendations for those seeking to decrease digital inequality among older adults in these communities through their own ICT classes

Identification of inhibitors of the Schistosoma mansoni VKR2 kinase domain

Schistosomiasis is a neglected tropical disease caused by parasitic flatworms. Current treatment relies on just one partially effective drug, praziquantel (PZQ). Schistosoma mansoni Venus Kinase Receptors 1 and 2 (SmVKR1 and SmVKR2) are important for parasite growth and egg production, and are potential targets for combating schistosomiasis. VKRs consist of an extracellular Venus Flytrap Module (VFTM) linked via a transmembrane helix to a kinase domain. Here, we initiated a drug discovery effort to inhibit the activity of the SmVKR2 kinase domain (SmVKR2KD) by screening the GSK published kinase inhibitor set 2 (PKIS2). We identified several inhibitors, of which four were able to inhibit its enzymatic activity and induced phenotypic changes in ex vivoS. mansoni. Our crystal structure of the SmVKR2KD displays an active-like state that sheds light on the activation process of VKRs. Our data provide a basis for the further exploration of SmVKR2 as a possible drug target

Structural and functional relationships in the virulence-associated cathepsin L proteases of the parasitic liver fluke, Fasciola hepatica

The helminth parasite Fasciola hepatica secretes cysteine proteases to facilitate tissue invasion, migration, and development within the mammalian host. The major proteases cathepsin L1 (FheCL1) and cathepsin L2 (FheCL2) were recombinantly produced and biochemically characterized. By using site-directed mutagenesis, we show that residues at position 67 and 205, which lie within the S2 pocket of the active site, are critical in determining the substrate and inhibitor specificity. FheCL1 exhibits a broader specificity and a higher substrate turnover rate compared with FheCL2. However, FheCL2 can efficiently cleave substrates with a Pro in the P2 position and degrade collagen within the triple helices at physiological pH, an activity that among cysteine proteases has only been reported forhuman cathepsin K. The 1.4-Å three-dimensional structure of the FheCL1 was determined by x-ray crystallography, and the three-dimensional structure of FheCL2 was constructed via homology-based modeling. Analysis and comparison of these structures and our biochemical data with those of human cathepsins L and Kprovided an interpretation of the substrate-recognition mechanisms of these major parasite proteases. Furthermore, our studies suggest that a configuration involving residue 67 and the "gatekeeper" residues 157 and 158 situated at the entrance of the active site pocket create a topology that endows FheCL2 with its unusual collagenolytic activity. The emergence of a specialized collagenolytic function in Fasciola likely contributes to the success of this tissue-invasive parasite. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc

Demonstration of the BioBaler harvesting system for collection of small-diameter woody biomass

As part of a project to investigate sustainable forest management practices for producing wood chips on the Oak Ridge Reservation (ORR) for the ORNL steam plant, the BioBaler was tested in various Oak Ridge locations in August of 2011. The purpose of these tests and the subsequent economic analysis was to determine the potential of this novel woody biomass harvesting method for collection of small-diameter, low value woody biomass. Results suggest that opportunities may exist for economical harvest of low-value and liability or negative-cost biomass. (e.g., invasives). This could provide the ORR and area land managers with a tool to produce feedstock while improving forest health, controlling problem vegetation, and generating local employment

Positive Selection Drives Preferred Segment Combinations during Influenza Virus Reassortment

Influenza A virus (IAV) has a segmented genome that allows for the exchange of genome segments between different strains. This reassortment accelerates evolution by breaking linkage, helping IAV cross species barriers to potentially create highly virulent strains. Challenges associated with monitoring the process of reassortment in molecular detail have limited our understanding of its evolutionary implications. We applied a novel deep sequencing approach with quantitative analysis to assess the in vitro temporal evolution of genomic reassortment in IAV. The combination of H1N1 and H3N2 strains reproducibly generated a new H1N2 strain with the hemagglutinin and nucleoprotein segments originating from H1N1 and the remaining six segments from H3N2. By deep sequencing the entire viral genome, we monitored the evolution of reassortment, quantifying the relative abundance of all IAV genome segments from the two parent strains over time and measuring the selection coefficients of the reassorting segments. Additionally, we observed several mutations coemerging with reassortment that were not found during passaging of pure parental IAV strains. Our results demonstrate how reassortment of the segmented genome can accelerate viral evolution in IAV, potentially enabled by the emergence of a small number of individual mutation