A multiplexed nanostructure-initiator mass spectrometry (NIMS) assay for simultaneously detecting glycosyl hydrolase and lignin modifying enzyme activities.

Lignocellulosic biomass is composed of three major biopolymers: cellulose, hemicellulose and lignin. Analytical tools capable of quickly detecting both glycan and lignin deconstruction are needed to support the development and characterization of efficient enzymes/enzyme cocktails. Previously we have described nanostructure-initiator mass spectrometry-based assays for the analysis of glycosyl hydrolase and most recently an assay for lignin modifying enzymes. Here we integrate these two assays into a single multiplexed assay against both classes of enzymes and use it to characterize crude commercial enzyme mixtures. Application of our multiplexed platform based on nanostructure-initiator mass spectrometry enabled us to characterize crude mixtures of laccase enzymes from fungi Agaricus bisporus (Ab) and Myceliopthora thermophila (Mt) revealing activity on both carbohydrate and aromatic substrates. Using time-series analysis we determined that crude laccase from Ab has the higher GH activity and that laccase from Mt has the higher activity against our lignin model compound. Inhibitor studies showed a significant reduction in Mt GH activity under low oxygen conditions and increased activities in the presence of vanillin (common GH inhibitor). Ultimately, this assay can help to discover mixtures of enzymes that could be incorporated into biomass pretreatments to deconstruct diverse components of lignocellulosic biomass.

Ionic Liquid Tolerance of Yeasts in Family Dipodascaceae and Genus Wickerhamomyces.

In previous studies of ionic liquid (IL) tolerance of numerous species of ascomycetous yeasts, two strains of Wickerhamomyces ciferrii and Galactomyces candidus had unusually high tolerance in media containing up to 5% (w/v) of the 1-ethyl-3-methylimidazolium acetate ([C2C1Im][OAc]). The study aimed at investigating whether additional strains of these species, and additional species in the Dipodascaceae family, also possess IL tolerance, and to compare sensitivity to the acetate and chloride versions of the ionic liquid. Fifty five yeast strains in the family Dipodascaceae, which encompasses genera Galactomyces, Geotrichum, and Dipodascus, and seven yeast strains of species Wickerhamomyces ciferrii were tested for ability to grow in laboratory medium containing no IL, 242 mM [C2C1Im][OAc], or 242 mM [C2C1Im]Cl, and in IL-pretreated switchgrass hydrolysate. Many yeasts exhibited tolerance of one or both ILs, with higher tolerance of the chloride anion than of the acetate anion. Different strains of the same species exhibited varying degrees of IL tolerance. Galactomyces candidus, UCDFSTs 52-260, and 50-64, had exceptionally robust growth in [C2C1Im][OAc], and also grew well in the switchgrass hydrolysate. Identification of IL tolerant and IL resistant yeast strains will facilitate studies of the mechanism of IL tolerance, which could include superior efflux, metabolism or exclusion.

Acquisition, Analysis, and Sharing of Data in 2015 and Beyond: A Survey of the Landscape: A Conference Report From the American Heart Association Data Summit 2015.

BACKGROUND: A 1.5-day interactive forum was convened to discuss critical issues in the acquisition, analysis, and sharing of data in the field of cardiovascular and stroke science. The discussion will serve as the foundation for the American Heart Association's (AHA's) near-term and future strategies in the Big Data area. The concepts evolving from this forum may also inform other fields of medicine and science. METHODS AND RESULTS: A total of 47 participants representing stakeholders from 7 domains (patients, basic scientists, clinical investigators, population researchers, clinicians and healthcare system administrators, industry, and regulatory authorities) participated in the conference. Presentation topics included updates on data as viewed from conventional medical and nonmedical sources, building and using Big Data repositories, articulation of the goals of data sharing, and principles of responsible data sharing. Facilitated breakout sessions were conducted to examine what each of the 7 stakeholder domains wants from Big Data under ideal circumstances and the possible roles that the AHA might play in meeting their needs. Important areas that are high priorities for further study regarding Big Data include a description of the methodology of how to acquire and analyze findings, validation of the veracity of discoveries from such research, and integration into investigative and clinical care aspects of future cardiovascular and stroke medicine. Potential roles that the AHA might consider include facilitating a standards discussion (eg, tools, methodology, and appropriate data use), providing education (eg, healthcare providers, patients, investigators), and helping build an interoperable digital ecosystem in cardiovascular and stroke science. CONCLUSION: There was a consensus across stakeholder domains that Big Data holds great promise for revolutionizing the way cardiovascular and stroke research is conducted and clinical care is delivered; however, there is a clear need for the creation of a vision of how to use it to achieve the desired goals. Potential roles for the AHA center around facilitating a discussion of standards, providing education, and helping establish a cardiovascular digital ecosystem. This ecosystem should be interoperable and needs to interface with the rapidly growing digital object environment of the modern-day healthcare system.

Environmental condition assessment of US military installations using GIS based spatial multi-criteria decision analysis.

Environment functions in various aspects including soil and water conservation, biodiversity and habitats, and landscape aesthetics. Comprehensive assessment of environmental condition is thus a great challenge. The issues include how to assess individual environmental components such as landscape aesthetics and integrate them into an indicator that can comprehensively quantify environmental condition. In this study, a geographic information systems based spatial multi-criteria decision analysis was used to integrate environmental variables and create the indicator. This approach was applied to Fort Riley Military installation in which land condition and its dynamics due to military training activities were assessed. The indicator was derived by integrating soil erosion, water quality, landscape fragmentation, landscape aesthetics, and noise based on the weights from the experts by assessing and ranking the environmental variables in terms of their importance. The results showed that landscape level indicator well quantified the overall environmental condition and its dynamics, while the indicator at level of patch that is defined as a homogeneous area that is different from its surroundings detailed the spatiotemporal variability of environmental condition. The environmental condition was mostly determined by soil erosion, then landscape fragmentation, water quality, landscape aesthetics, and noise. Overall, environmental condition at both landscape and patch levels greatly varied depending on the degree of ground and canopy disturbance and their spatial patterns due to military training activities and being related to slope. It was also determined the environment itself could be recovered quickly once military training was halt or reduced. Thus, this study provided an effective tool for the army land managers to monitor environmental dynamics and plan military training activities. Its limitation lies at that the obtained values of the indicator vary and are subjective to the experts' knowledge and experience. Thus, further advancing this approach is needed by developing a scientific method to derive the weights of environmental variables.

Dental arch relationship outcomes in children with complete unilateral cleft lip and palate treated at Princess Margaret Hospital for Children, Perth, Western Australia.

OBJECTIVES: To (1) audit dental arch relationships of all children born between 1982 and 1999 with complete unilateral cleft lip and palate (UCLP) treated at the Cleft Lip and Palate Unit, Princess Margaret Hospital for Children (PMH), Perth, Western Australia, (2) assess the distribution of GOSLON ratings from dental casts taken at 9 years, (3) compare the 9-year GOSLON ratings for "High" and "Low" caseload surgeons, and (4) compare the 9-year PMH GOSLON ratings with published ratings from other units. DESIGN: Retrospective audit of dental casts and medical charts. PATIENTS: Dental casts were retrieved for 71 children (47 boys and 24 girls) at 9 years of age. MAIN OUTCOME MEASURES: GOSLON ratings. RESULTS: Sixty-eight percent of patients had an excellent to satisfactory dental arch relationship (GOSLON Yardstick ratings 1 to 3) at 9 years with a mean rating of 2.85. High caseload surgeons achieved statistically better mean GOSLON ratings than low caseload surgeons (2.72 and 3.33, respectively). CONCLUSIONS: PMH Cleft Unit's dental arch relationship outcomes are comparable to published series of units using similar treatment protocols. High caseload surgeons achieved better dental arch relationships than low caseload surgeons.

The influence of orthodontic treatment on the Goslon score of unilateral cleft lip and palate patients.

OBJECTIVE: To assess the effect of orthodontic treatment on Goslon Yardstick outcome. DESIGN: Retrospective study. PATIENTS: A series of 66 consecutive patients born with a complete unilateral left lip and palate. Patients were sorted into a nontreatment group (n  =  47) and a treatment group (n  =  19). METHOD: Three assessors trained in the use of the Goslon Yardstick ranked the dental arch relationships of study casts taken at 6 and 9 years. RESULTS: There was only a fair agreement (κ  =  .33) between 6- and 9-year Goslon Yardstick scores for the cohort of 66 patients, with a significant (p < .05) difference in the mean score at 6 years (3.17 ± 0.8) and at 9 years (2.88 ± 1.0). Removal of 19 subjects who had orthodontic inventions prior to taking of the 9-year-old study cast improved the agreement to moderate (κ  =  .52). There was no significant difference (p > .05) in mean scores at 6 and 9 years (3.13 ± 0.9 and 3.17 ± 1.03, respectively). The treatment group exhibited significant differences (p < .001) with mean Goslon Yardstick scores of 3.0 ± 0.9 at 6 and 2.25 ± 0.45 at 9 years. CONCLUSIONS: The inclusion of patients who had received orthodontic treatment prior to taking of study casts being used for Goslon Yardstick scoring can result in a more favorable outcome. Patients who have received active orthodontic treatment prior to taking of dental casts should be excluded or accounted for in audits to assess primary cleft surgical outcome in patients with a unilateral cleft lip and palate.

Why isn't bupropion the most frequently prescribed antidepressant?

OBJECTIVE: Reviews of antidepressant medication efficacy suggest that all antidepressants are equally effective. Bupropion is less likely than other antidepressants to cause weight gain and sexual dysfunction, the 2 side effects that are of greatest concern to patients and that have the greatest impact on long-term compliance. If bupropion is as effective as other antidepressants, and it does not cause the side effects that are the most frequent causes of long-term noncompliance, then why isn't it the most frequently prescribed antidepressant medication? To understand psychiatrists' decision making at the time an antidepressant is chosen, we conducted the Rhode Island Factors Associated With Antidepressant Choice Survey (FAACS). METHOD: For 1137 DSM-IV-diagnosed depressed patients initiated on an antidepressant, the treating psychiatrist completed a 43-item questionnaire listing factors that might have influenced the choice of medication. The questionnaire was filled out immediately after the antidepressant was prescribed to treat a depressive disorder. This study was conducted from August 2001 to February 2002. RESULTS: Because the reasons for choosing a medication to augment an existing regimen might be different from those used in monotherapy, augmentation trials were excluded from the analysis, leaving a sample of 965 patients. Bupropion was rarely prescribed when the presence of comorbid anxiety disorders or symptoms reflecting central nervous system activation influenced antidepressant selection. When the desire to avoid side effects, especially sexual dysfunction and weight gain, were the basis of selection, then bupropion was significantly more often prescribed than other antidepressants (p < .001). CONCLUSIONS: Although there is little evidence that patient factors predict differential medication response, psychiatrists are strongly inclined to base antidepressant selection on clinical profiles and avoid prescribing bupropion for depressed patients with high anxiety. Possible reasons for the discrepancy between psychiatrists' prescribing habits and the results of empirical study are discussed.

Which factors influence psychiatrists' selection of antidepressants?

OBJECTIVE: There is little empirical evidence to guide clinicians in choosing among the diverse array of antidepressants available. In the absence of replicated empirical research guiding the selection of antidepressants, it is of interest to examine what factors psychiatrists consider when prescribing antidepressants. METHOD: For 1,137 depressed patients who received a new antidepressant prescription, the treating psychiatrist completed a 43-item questionnaire listing factors that might have influenced the choice of antidepressant medication. The questionnaire was filled out immediately after an antidepressant was prescribed to treat a depressive disorder. RESULTS: The most common factors influencing antidepressant selection were the avoidance of specific side effects, the presence of comorbid psychiatric disorders, and the presence of specific clinical symptoms. Prior treatment history, including prior positive or failed response to a drug, was the next most frequently endorsed factor influencing medication choice. Some factors that have been commonly discussed in the literature, such as concern about discontinuation syndrome and drug-drug interactions, rarely influenced antidepressant selection. CONCLUSIONS: Because relatively little research has examined clinical features associated with differential response to the newer generation of antidepressants, a study of psychiatrists' prescribing practices highlights priorities for future controlled research. Our results suggest that two priority areas are the treatment of depression with coexisting anxiety symptoms/anxiety disorders and the influence of particular symptoms on response to different medications.