924 research outputs found
Re-imagining Your Professional Boundaries and Future Patrons: Are You Ready for Your Second Life?
Question/Purpose: To describe and demonstrate the virtual online world Second Life (SL) in the context of education, library, and health seeking behavior. Setting/Participants: An educator, a librarian, and a health seeking SL resident participate in a learner -oriented vignette on the SL Health Info Island. Brief Description: The authors will briefly describe the online virtual world SL, the relevant information seeking uses of the world, how the authors became interested in applying the online setting to health education and information dissemination, a few of the technological and social shortcomings of the site, and show a pre-recorded health education vignette in SL. Outcome: Over 7 million people worldwide have experienced SL. In many ways, the SL residents are using the virtual world in a manner similar to the geographically bounded world: meeting and communicating life experiences with new people, participating in an astonishing variety of educational sessions, and seeking informed and meaningful interaction with health professionals. Conclusion: As the world matures and SL locations become standardized with rules and interaction protocols, there will be a definite need for accurate and timely informational exchanges. There is already an information revolution occurring in SL, are you ready?https://digitalrepository.unm.edu/hslic-posters-presentations/1042/thumbnail.jp
Target Zones in History and Theory: Lessons from an Austro-Hungarian Experiment (1896-1914)
The first known experiment with an exchange rate band took place in Austria-
Hungary between 1896 and 1914. The rationale for introducing this policy rested
on precisely those intuitions that the modern literature has emphasized: the band
was designed to secure both exchange rate stability and monetary policy
autonomy. However, unlike more recent experiences, such as the ERM, this
policy was not undermined by credibility problems. The episode provides an ideal
testing ground for some important ideas in modern macroeconomics: specifically,
can formal rules, when faithfully adhered to, provide policy makers with some
advantages such as short term autonomy? First, we find that a credible band has a
"microeconomic" influence on exchange rate stability. By reducing uncertainty, a
credible fluctuation band improves the quality of expectations, a channel that has been neglected in the modern literature. Second, we show that the standard test of the basic target zone model is flawed and develop an alternative methodology. We believe that these findings shed a new light on the economics of exchange rate bands
Two Earth-sized planets orbiting Kepler-20
Since the discovery of the first extrasolar giant planets around Sun-like
stars, evolving observational capabilities have brought us closer to the
detection of true Earth analogues. The size of an exoplanet can be determined
when it periodically passes in front of (transits) its parent star, causing a
decrease in starlight proportional to its radius. The smallest exoplanet
hitherto discovered has a radius 1.42 times that of the Earth's radius (R
Earth), and hence has 2.9 times its volume. Here we report the discovery of two
planets, one Earth-sized (1.03R Earth) and the other smaller than the Earth
(0.87R Earth), orbiting the star Kepler-20, which is already known to host
three other, larger, transiting planets. The gravitational pull of the new
planets on the parent star is too small to measure with current
instrumentation. We apply a statistical method to show that the likelihood of
the planetary interpretation of the transit signals is more than three orders
of magnitude larger than that of the alternative hypothesis that the signals
result from an eclipsing binary star. Theoretical considerations imply that
these planets are rocky, with a composition of iron and silicate. The outer
planet could have developed a thick water vapour atmosphere.Comment: Letter to Nature; Received 8 November; accepted 13 December 2011;
Published online 20 December 201
Multi-Institutional FASTQ File Exchange as a Means of Proficiency Testing for Next-Generation Sequencing Bioinformatics and Variant Interpretation
Next-generation sequencing is becoming increasingly common in clinical laboratories worldwide and is revolutionizing clinical molecular testing. However, the large amounts of raw data produced by next-generation sequencing assays and the need for complex bioinformatics analyses present unique challenges. Proficiency testing in clinical laboratories has traditionally been designed to evaluate assays in their entirety; however, it can be alternatively applied to separate assay components. We developed and implemented a multi-institutional proficiency testing approach to directly assess custom bioinformatics and variant interpretation processes. Six clinical laboratories, all of which use the same commercial library preparation kit for next-generation sequencing analysis of tumor specimens, each submitted raw data (FASTQ files) from four samples. These 24 file sets were then deidentified and redistributed to five of the institutions for analysis and interpretation according to their clinically validated approach. Among the laboratories, there was a high rate of concordance in the calling of single-nucleotide variants, in particular those we considered clinically significant (100% concordance). However, there was significant discordance in the calling of clinically significant insertions/deletions, with only two of seven being called by all participating laboratories. Missed calls were addressed by each laboratory to improve their bioinformatics processes. Thus, through our alternative proficiency testing approach, we identified the bioinformatic detection of insertions/deletions as an area of particular concern for clinical laboratories performing next-generation sequencing testing
Effectiveness of pharmacological treatments for severe agitation in real-world emergency settings: protocol of individual-participant-data network meta-analysis.
BACKGROUND
Severe psychomotor agitation and aggression often require immediate pharmacological intervention, but clear evidence-based recommendations for choosing among the multiple options are lacking. To address this gap, we plan a systematic review and individual-participant-data network meta-analysis to investigate their comparative effectiveness in real-world emergency settings with increased precision.
METHODS
We will include randomized controlled trials investigating intramuscular or intravenous pharmacological interventions, as monotherapy or in combination, in adults with severe psychomotor agitation irrespective of the underlying diagnosis and requiring rapid tranquilization in general or psychiatric emergency settings. We will exclude studies before 2002, those focusing on specific reasons for agitation and placebo-controlled trials to avoid concerns related to the transitivity assumption and potential selection biases. We will search for eligible studies in BIOSIS, CENTRAL, CINAHL Plus, Embase, LILACS, MEDLINE via Ovid, PubMed, ProQuest, PsycINFO, ClinicalTrials.gov, and WHO-ICTRP. Individual-participant data will be requested from the study authors and harmonized into a uniform format, and aggregated data will also be extracted from the studies. At least two independent reviewers will conduct the study selection, data extraction, risk-of-bias assessment using RoB 2, and applicability evaluation using the RITES tool. The primary outcome will be the number of patients achieving adequate sedation within 30 min after treatment, with secondary outcomes including the need for additional interventions and adverse events, using odds ratios as the effect size. If enough individual-participant data will be collected, we will synthesize them in a network meta-regression model within a Bayesian framework, incorporating study- and participant-level characteristics to explore potential sources of heterogeneity. In cases where individual-participant data are unavailable, potential data availability bias will be explored, and models allowing for the inclusion of studies reporting only aggregated data will be considered. We will assess the confidence in the evidence using the Confidence in Network Meta-Analysis (CINeMA) approach.
DISCUSSION
This individual-participant-data network meta-analysis aims to provide a fine-tuned synthesis of the evidence on the comparative effectiveness of pharmacological interventions for severe psychomotor agitation in real-world emergency settings. The findings from this study can greatly be provided clearer evidence-based guidance on the most effective treatments.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42023402365
Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.
BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution
Transcriptome analyses of mouse and human mammary cell subpopulations reveal multiple conserved genes and pathways
INTRODUCTION: Molecular characterization of the normal epithelial cell types that reside in the mammary gland is an important step toward understanding pathways that regulate self-renewal, lineage commitment, and differentiation along the hierarchy. Here we determined the gene expression signatures of four distinct subpopulations isolated from the mouse mammary gland. The epithelial cell signatures were used to interrogate mouse models of mammary tumorigenesis and to compare with their normal human counterpart subsets to identify conserved genes and networks. METHODS: RNA was prepared from freshly sorted mouse mammary cell subpopulations (mammary stem cell (MaSC)-enriched, committed luminal progenitor, mature luminal and stromal cell) and used for gene expression profiling analysis on the Illumina platform. Gene signatures were derived and compared with those previously reported for the analogous normal human mammary cell subpopulations. The mouse and human epithelial subset signatures were then subjected to Ingenuity Pathway Analysis (IPA) to identify conserved pathways. RESULTS: The four mouse mammary cell subpopulations exhibited distinct gene signatures. Comparison of these signatures with the molecular profiles of different mouse models of mammary tumorigenesis revealed that tumors arising in MMTV-Wnt-1 and p53-/- mice were enriched for MaSC-subset genes, whereas the gene profiles of MMTV-Neu and MMTV-PyMT tumors were most concordant with the luminal progenitor cell signature. Comparison of the mouse mammary epithelial cell signatures with their human counterparts revealed substantial conservation of genes, whereas IPA highlighted a number of conserved pathways in the three epithelial subsets. CONCLUSIONS: The conservation of genes and pathways across species further validates the use of the mouse as a model to study mammary gland development and highlights pathways that are likely to govern cell-fate decisions and differentiation. It is noteworthy that many of the conserved genes in the MaSC population have been considered as epithelial-mesenchymal transition (EMT) signature genes. Therefore, the expression of these genes in tumor cells may reflect basal epithelial cell characteristics and not necessarily cells that have undergone an EMT. Comparative analyses of normal mouse epithelial subsets with murine tumor models have implicated distinct cell types in contributing to tumorigenesis in the different models
Identification of a PA-Binding Peptide with Inhibitory Activity against Influenza A and B Virus Replication
There is an urgent need for new drugs against influenza type A and B viruses due to incomplete protection by vaccines and the emergence of resistance to current antivirals. The influenza virus polymerase complex, consisting of the PB1, PB2 and PA subunits, represents a promising target for the development of new drugs. We have previously demonstrated the feasibility of targeting the protein-protein interaction domain between the PB1 and PA subunits of the polymerase complex of influenza A virus using a small peptide derived from the PA-binding domain of PB1. However, this influenza A virus-derived peptide did not affect influenza B virus polymerase activity. Here we report that the PA-binding domain of the polymerase subunit PB1 of influenza A and B viruses is highly conserved and that mutual amino acid exchange shows that they cannot be functionally exchanged with each other. Based on phylogenetic analysis and a novel biochemical ELISA-based screening approach, we were able to identify an influenza A-derived peptide with a single influenza B-specific amino acid substitution which efficiently binds to PA of both virus types. This dual-binding peptide blocked the viral polymerase activity and growth of both virus types. Our findings provide proof of principle that protein-protein interaction inhibitors can be generated against influenza A and B viruses. Furthermore, this dual-binding peptide, combined with our novel screening method, is a promising platform to identify new antiviral lead compounds
Attitudes and Acceptance of Oral and Parenteral HIV Preexposure Prophylaxis among Potential User Groups: A Multinational Study
BACKGROUND: The use of antiviral medications by HIV negative people to prevent acquisition of HIV or pre-exposure prophylaxis (PrEP) has shown promising results in recent trials. To understand the potential impact of PrEP for HIV prevention, in addition to efficacy data, we need to understand both the acceptability of PrEP among members of potential user groups and the factors likely to determine uptake. METHODS AND FINDINGS: Surveys of willingness to use PrEP products were conducted with 1,790 members of potential user groups (FSWs, MSM, IDUs, SDCs and young women) in seven countries: Peru, Ukraine, India, Kenya, Botswana, Uganda and South Africa. Analyses of variance were used to assess levels of acceptance across different user groups and countries. Conjoint analysis was used to examine the attitudes and preferences towards hypothetical and known attributes of PrEP programs and medications. Overall, members of potential user groups were willing to consider taking PrEP (61% reported that they would definitely use PrEP). Current results demonstrate that key user groups in different countries perceived PrEP as giving them new possibilities in their lives and would consider using it as soon as it becomes available. These results were maintained when subjects were reminded of potential side effects, the need to combine condom use with PrEP, and for regular HIV testing. Across populations, route of administration was considered the most important attribute of the presented alternatives. CONCLUSIONS: Despite multiple conceivable barriers, there was a general willingness to adopt PrEP in key populations, which suggests that if efficacious and affordable, it could be a useful tool in HIV prevention. There would be a willingness to experience inconvenience and expense at the levels included in the survey. The results suggest that delivery in a long lasting injection would be a good target in drug development
Validation of MIPAS ClONO2 measurements
Altitude profiles of ClONO2 retrieved with the IMK (Institut fur Meteorologie und Klimaforschung) science-oriented data processor from MIPAS/Envisat (Michelson Interferometer for Passive Atmospheric Sounding on Envisat) mid-infrared limb emission measurements between July 2002 and March 2004 have been validated by comparison with balloon-borne (Mark IV, FIRS2, MIPAS-B), airborne (MIPAS-STR), ground-based (Spitsbergen, Thule, Kiruna, Harestua, Jungfraujoch, Izana, Wollongong, Lauder), and spaceborne (ACE-FTS) observations. With few exceptions we found very good agreement between these instruments and MIPAS with no evidence for any bias in most cases and altitude regions. For balloon-borne measurements typical absolute mean differences are below 0.05 ppbv over the whole altitude range from 10 to 39 km. In case of ACE-FTS observations mean differences are below 0.03 ppbv for observations below 26 km. Above this altitude the comparison with ACE-FTS is affected by the photochemically induced diurnal variation of ClONO2. Correction for this by use of a chemical transport model led to an overcompensation of the photochemical effect by up to 0.1 ppbv at altitudes of 30-35 km in case of MIPAS-ACE-FTS comparisons while for the balloon-borne observations no such inconsistency has been detected. The comparison of MIPAS derived total column amounts with ground-based observations revealed no significant bias in the MIPAS data. Mean differences between MIPAS and FTIR column abundances are 0.11 +/- 0.12 x 10(14) cm(-2) (1.0 +/- 1.1%) and -0.09 +/- 0.19 x 10(14) cm(-2) (-0.8 +/- 1.7%), depending on the coincidence criterion applied. chi(2) tests have been performed to assess the combined precision estimates of MIPAS and the related instruments. When no exact coincidences were available as in case of MIPAS-FTIR or MIPAS-ACE-FTS comparisons it has been necessary to take into consideration a coincidence error term to account for chi(2) deviations. From the resulting chi(2) profiles there is no evidence for a systematic over/underestimation of the MIPAS random error analysis.Peer reviewe
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