Detection and identification of 700 drugs by multi-target screening with a 3200 Q TRAP LC-MS/MS system and library searching

The multi-target screening method described in this work allows the simultaneous detection and identification of 700 drugs and metabolites in biological fluids using a hybrid triple-quadrupole linear ion trap mass spectrometer in a single analytical run. After standardization of the method, the retention times of 700 compounds were determined and transitions for each compound were selected by a "scheduled" survey MRM scan, followed by an information-dependent acquisition using the sensitive enhanced product ion scan of a Q TRAP hybrid instrument. The identification of the compounds in the samples analyzed was accomplished by searching the tandem mass spectrometry (MS/MS) spectra against the library we developed, which contains electrospray ionization-MS/MS spectra of over 1,250 compounds. The multi-target screening method together with the library was included in a software program for routine screening and quantitation to achieve automated acquisition and library searching. With the help of this software application, the time for evaluation and interpretation of the results could be drastically reduced. This new multi-target screening method has been successfully applied for the analysis of postmortem and traffic offense samples as well as proficiency testing, and complements screening with immunoassays, gas chromatography-mass spectrometry, and liquid chromatography-diode-array detection. Other possible applications are analysis in clinical toxicology (for intoxication cases), in psychiatry (antidepressants and other psychoactive drugs), and in forensic toxicology (drugs and driving, workplace drug testing, oral fluid analysis, drug-facilitated sexual assault)

Building Resilience Through Strengths-Based Learning During Graduate Study Abroad: An Exploratory Study

Resilience has been identified as an essential skill for leaders (Basso, Gruendel, Key, MacBlaine, & Reynolds, 2015) and as crucial for navigating both school and life challenges (Yeager & Dweck, 2012). Research indicates that there are a variety of ways to build resilience, including in educational settings (Yeager & Dweck, 2012). Higher education institutions utilize pedagogical practices to maximize student learning and growth opportunities (Rennick, 2015). One pedagogical frame often employed is experiential education. College and university faculty have embedded experiential learning pedagogy in the curriculum to facilitate learning outside the classroom (Liang, Caton, & Hill, 2015; Jordan, Gagnon, Anderson, & Pilcher, 2018; Towers & Loyness, 2018). Additionally, experiential education principles have been integrated with study abroad curriculum to support student learning (Harper, 2018; Pipitone and Raghaven, 2017; Pipitone, 2018). Educators are interested in learning more about the potential effect of strengths-based initiatives in higher education (Soria & Stubblefield, 2015a). While scholars have reported on the benefits of utilizing a strengths-based curriculum for personal development (Passerilli, Hall, & Anderson, 2010), much work is still needed to explore the potential outcomes of strengths-based education on resilience development. This research sought to address the gap in the literature using a short-term graduate study abroad program embedded with experiential education practices to examine how the pedagogy design contributed to students’ perceived growth in resilience. The strengths-based curricular design included approximately sixty hours of strengths-based instruction prior to the trip and fourteen days of applying the common strengths language to enhance learning experiences and mitigate challenges

The MOLE Drilling Project: Laboratory at Depth on an Active Fault in Central Italy

Several fundamental questions concerning: i) the geophysical and geochemical processes controlling normal faulting and earthquake ruptures during moderate-to-large seismic events and ii) the low angle normal fault paradox, still need to be fully answered. In this work we aim to present an example of low angle normal fault (Alto Tiberina Fault) located in the Northern Apennines (Italy) showing conclusive evidence of its seismic activity. This fault is a likely target of an international project: the MOLE (Multidisciplinary Observatory and Laboratory of Experiments) Drilling project. Indeed, under the auspices of the International Continental Scientific Drilling Program a workshop is being organized in Italy next spring 2008, to promote the creation of an international multidisciplinary team of scientists, to discuss the project in detail and also to prepare a full proposal for ICDP. This project wants to investigate the inner structure of normal faults in Central Italy to get physical constraints on the processes controlling faulting and earthquake mechanics. The Umbria-Marche sector of Northern Apennines offers a unique opportunity to reach a complex system of normal faults among which we selected two possible targets. 1) The active Colfiorito fault dipping about 45° toward SW which Tiberina low angle normal fault dipping 15°-25° towards ENE, which moves through a combination of aseismic creep and repeating microearthquakes. Drilling the Colfiorito active fault at a depth of about 2-3 km allows targeting the high coseismic slip patch of the 1997 earthquake M=6 seismogenic structure. Drilling the Alto Tiberina Fault at a depth of nearly 5-6 km will target a micro seismicity source. We aim to collect new original data through borehole logging and sampling and to set up a permanent observatory at depth for a multidisciplinary monitoring to characterize these active normal fault zones. This will allow to understand how such faults behave and to create more realistic models of: earthquake nucleation, seismicity pattern, stress interactions and earthquake triggering at local and regional scale. Both drilling targets present relevant technical issues that should be discussed from different points of view before selecting the starting drilling site

Fuelwood savings and carbon emission reductions by the use of improved cooking stoves in an Afromontane forest, Ethiopia

In many Sub-Saharan African countries, fuelwood collection is among the most important drivers of deforestation and particularly forest degradation. In a detailed field study in the Kafa region of southern Ethiopia, we assessed the potential of efficient cooking stoves to mitigate the negative impacts of fuelwood harvesting on forests. Eleven thousand improved cooking stoves (ICS), specifically designed for baking Ethiopia’s staple food injera, referred to locally as “Mirt” stoves, have been distributed here. We found a high acceptance rate of the stove. One hundred forty interviews, including users and non-users of the ICS, revealed fuelwood savings of nearly 40% in injera preparation compared to the traditional three-stone fire, leading to a total annual savings of 1.28 tons of fuelwood per household. Considering the approximated share of fuelwood from unsustainable sources, these savings translate to 11,800 tons of CO2 saved for 11,156 disseminated ICS, corresponding to the amount of carbon stored in over 30 ha of local forest. We further found that stove efficiency increased with longer injera baking sessions, which shows a way of optimizing fuelwood savings by adapted usage of ICS. Our study confirms that efficient cooking stoves, if well adapted to the local cooking habits, can make a significant contribution to the conservation of forests and the avoidance of carbon emission from forest clearing and degradation

Hamlet and the fall of the Berlin wall : the myth of interventionist Shakespeare performance

The critical reception of Heiner Müller’s 1990 Hamlet/Maschine at the Deutsches Theater in East Berlin epitomizes a trend of crediting GDR Shakespeare performance with political influence. Drawing on rehearsal notes and reviews, Oliver challenges the interventionist Shakespeare myth, contrasting the Deutsches Theater’s political involvement with the impact of its Hamlet production on events surrounding the fall of the Berlin Wall. Shakespeare’s capacity for political intervention at this point was limited by theater practitioners’ reliance on public funding, their close relationships with governmental authority, and an underlying distrust of the masses. Ultimately, GDR artists proved useful to the 1989 protest movement because they occupied a unique position at the interface of dissidence and power

Interventions to prevent injuries in construction workers

Background Construction workers are frequently exposed to various types of injury-inducing hazards. A number of injury prevention interventions have been proposed, yet their effectiveness is uncertain. Objectives To assess the effects of interventions to prevent injuries in construction workers. Search methods We searched the Cochrane Injuries Group’s specialised register, CENTRAL,MEDLINE, EMBASE, PsycINFO,OSH-ROM(including NIOSHTIC and HSELINE), Scopus, Web of Science and EI Compendex to September 2011. The searches were not restricted by language or publication status. The reference lists of relevant papers and reviews were also searched. Selection criteria Randomised controlled trials, controlled before-after (CBA) studies and interrupted time series (ITS) of all types of interventions for preventing fatal and non-fatal injuries among workers at construction sites. Data collection and analysis Two review authors independently selected studies, extracted data and assessed study quality. For ITS, we re-analysed the studies and used an initial effect, measured as the change in injury-rate in the year after the intervention, as well as a sustained effect, measured as the change in time trend before and after the intervention

Is team sport the key to getting everybody active, every day? A systematic review of physical activity interventions aimed at increasing girls' participation in team sport

Background: It is estimated that 21% of boys and 16% of girls in England meet recommended physical activity guidelines. Team sport has the potential to increase physical activity levels; however, studies show that gender-based factors can influence girls’ participation in team sport. Furthermore, evidence for the effectiveness of interventions promoting team sport among girls is limited. This systematic review aimed to assess the impact of physical activity interventions on secondary school-aged girls’ (aged 11-18 years) participation in team sport and to identify potential strategies for increasing participation. Methods: Electronic databases and grey literature were systematically searched for studies of interventions targeting team sport participation among girls in the UK. Results were exported to Refworks, duplicates removed and eligible studies identified. Extracted data included: participant details, such as sample size and age; components of the intervention; outcomes assessed; and each study was quality appraised. Due to heterogeneity across studies, results were presented narratively. Results: Four studies sourced from the grey literature met the inclusion criteria. Findings suggest that physical activity interventions can encourage girls to try new sports, but evidence is limited in relation to sustained participation. Potential strategies for promoting participation included: consultation with girls, implementation of appropriate peer-leaders and friendship group strategies, early intervention and consideration of intervention setting. Conclusions: This review highlights the limited availability of evidence on the effectiveness of physical activity interventions for promoting team sport participation among girls in the UK. Findings indicate that future research is needed to improve the methodological quality of complex intervention evaluation. Physical activity interventions may have the potential to encourage girls to try team sport, but their impact on sustained participation, and subsequent physical activity outcomes, is less apparent

Validity of the Dictionary of Occupational Titles for Assessing Upper Extremity Work Demands

Objectives: The Dictionary of Occupational Titles (DOT) is used in vocational rehabilitation to guide decisions about the ability of a person with activity limitations to perform activities at work. The DOT has categorized physical work demands in five categories. The validity of this categorization is unknown. Aim of this study was to investigate whether the DOT could be used validly to guide decisions for patients with injuries to the upper extremities. Four hypotheses were tested. Methods: A database including 701 healthy workers was used. All subjects filled out the Dutch Musculoskeletal Questionnaire, from which an Upper Extremity Work Demands score (UEWD) was derived. First, relation between the DOT-categories and UEWD-score was analysed using Spearman correlations. Second, variance of the UEWD-score in occupational groups was tested by visually inspecting boxplots and assessing kurtosis of the distribution. Third, it was investigated whether occupations classified in one DOT-category, could significantly differ on UEWD-scores. Fourth, it was investigated whether occupations in different DOT-categories could have similar UEWD-scores using Mann Whitney U-tests (MWU). Results: Relation between the DOT-categories and the UEWD-score was weak (r(sp) = 0.40; p < .01). Overlap between categories was found. Kurtosis exceeded +/- 1.0 in 3 occupational groups, indicating large variance. UEWD-scores were significantly different within one DOT-category (MWU = 1.500; p < .001). UEWD scores between DOT-categories were not significantly different (MWU = 203.000; p = .49). Conclusion: All four hypotheses could not be rejected. The DOT appears to be invalid for assessing upper extremity work demands

Universal Quake Statistics: From Compressed Nanocrystals to Earthquakes

Slowly-compressed single crystals, bulk metallic glasses (BMGs), rocks, granular materials, and the earth all deform via intermittent slips or “quakes”. We find that although these systems span 12 decades in length scale, they all show the same scaling behavior for their slip size distributions and other statistical properties. Remarkably, the size distributions follow the same power law multiplied with the same exponential cutoff. The cutoff grows with applied force for materials spanning length scales from nanometers to kilometers. The tuneability of the cutoff with stress reflects “tuned critical” behavior, rather than self-organized criticality (SOC), which would imply stress-independence. A simple mean field model for avalanches of slipping weak spots explains the agreement across scales. It predicts the observed slip-size distributions and the observed stress-dependent cutoff function. The results enable extrapolations from one scale to another, and from one force to another, across different materials and structures, from nanocrystals to earthquakes

Merged consensus clustering to assess and improve class discovery with microarray data

<p>Abstract</p> <p>Background</p> <p>One of the most commonly performed tasks when analysing high throughput gene expression data is to use clustering methods to classify the data into groups. There are a large number of methods available to perform clustering, but it is often unclear which method is best suited to the data and how to quantify the quality of the classifications produced.</p> <p>Results</p> <p>Here we describe an R package containing methods to analyse the consistency of clustering results from any number of different clustering methods using resampling statistics. These methods allow the identification of the the best supported clusters and additionally rank cluster members by their fidelity within the cluster. These metrics allow us to compare the performance of different clustering algorithms under different experimental conditions and to select those that produce the most reliable clustering structures. We show the application of this method to simulated data, canonical gene expression experiments and our own novel analysis of genes involved in the specification of the peripheral nervous system in the fruitfly, <it>Drosophila melanogaster</it>.</p> <p>Conclusions</p> <p>Our package enables users to apply the merged consensus clustering methodology conveniently within the R programming environment, providing both analysis and graphical display functions for exploring clustering approaches. It extends the basic principle of consensus clustering by allowing the merging of results between different methods to provide an averaged clustering robustness. We show that this extension is useful in correcting for the tendency of clustering algorithms to treat outliers differently within datasets. The R package, <it>clusterCons</it>, is freely available at CRAN and sourceforge under the GNU public licence.</p