Improving antibiotic prescribing for children in the resource-poor setting.

Antibiotics are a critically important part of paediatric medical care in low- and middle-income countries (LMICs), where infectious diseases are the leading cause of child mortality. The World Health Organization estimates that >50% of all medicines are prescribed, dispensed or sold inappropriately and that half of all patients do not take their medicines correctly. Given the rising prevalence of antimicrobial resistance globally, inappropriate antibiotic use is of international concern, and countries struggle to implement basic policies promoting rational antibiotic use. Many barriers to rational paediatric prescribing in LMICs persist. The World Health Organization initiatives, such as 'Make medicines child size', the Model List of Essential Medicines for Children and the Model Formulary for Children, have been significant steps forward. Continued strategies to improve access to appropriate drugs and formulations, in conjunction with improved evidence-based clinical guidelines and dosing recommendations, are essential to the success of such initiatives on both a national and an international level. This paper provides an overview of these issues and considers future developments that may improve LMIC antibiotic prescribing

It\u27s Too Late to Be Sorry Now.

Photo of Henri Therrien; Illustration of lady cryinghttps://scholarsjunction.msstate.edu/cht-sheet-music/9350/thumbnail.jp

PAHs in the Halo of NGC 5529

We present sensitive ISO $\lambda 6.7 \mu$m observations of the edge-on galaxy, NGC 5529, finding an extensive MIR halo around NGC 5529. The emission is dominated by PAHs in this band. The PAH halo has an exponential scale height of 3.7 kpc but can still be detected as far as $\approx 10$ kpc from the plane to the limits of the high dynamic range (1770/1) data. This is the most extensive PAH halo yet detected in a normal galaxy. This halo shows substructure and the PAHs likely originate from some type of disk outflow. PAHs are long-lived in a halo environment and therefore continuous replenishment from the disk is not required (unless halo PAHs are also being destroyed or removed), consistent with the current low SFR of the galaxy. The PAHs correlate spatially with halo H$\alpha$ emission, previously observed by Miller & Veilleux (2003); both components are likely excited/ionized by in-disk photons that are leaking into the halo. The presence of halo gas may be related to the environment of NGC 5529 which contains at least 17 galaxies in a small group of which NGC 5529 is the dominant member. Of these, we have identified two new companions from the SDSS.Comment: 16 pages, 5 gif figures, accepted for publication in A&A, For pdf with higher quality figures, see http://www.astro.queensu.ca/~irwi

A Multi-Wavelength Infrared Study of NGC 891

We present a multi-wavlength infrared study of the nearby, edge-on, spiral galaxy NGC 891. We have examined 20 independent, spatially resolved IR images of this galaxy, 14 of which are newly reduced and/or previously unpublished images. These images span a wavelength regime from 1.2 microns in which the emission is dominated by cool stars, through the MIR, in which emission is dominated by PAHs, to 850 microns, in which emission is dominated by cold dust in thermal equilibrium with the radiation field. The changing morphology of the galaxy with wavelength illustrates the changing dominant components. We detect extra-planar dust emission in this galaxy, consistent with previously published results, but now show that PAH emission is also in the halo, to a vertical distance of z >= 2.5 kpc. We compare the vertical extents of various components and find that the PAHs (from 7.7 and 8 micron data) and warm dust (24 microns) extend to smaller z heights than the cool dust (450 microns). For six locations in the galaxy for which the S/N was sufficient, we present SEDs of the IR emission, including two in the halo - the first time a halo SED in an external galaxy has been presented. We have modeled these SEDs and find that the PAH fraction is similar to Galactic values (within a factor of two), with the lowest value at the galaxy's center, consistent with independent results of other galaxies. In the halo environment, the fraction of dust exposed to a colder radiation field, is of order unity, consistent with an environment in which there is no star formation. The source of excitation is likely from photons escaping from the disk.Comment: 24 pages, 17 figures, 7 tables, accepted for publication in MNRA

Young Exoplanet Transit Initiative (YETI)

We present the Young Exoplanet Transit Initiative (YETI), in which we use several 0.2 to 2.6m telescopes around the world to monitor continuously young (< 100 Myr), nearby (< 1 kpc) stellar clusters mainly to detect young transiting planets (and to study other variability phenomena on time-scales from minutes to years). The telescope network enables us to observe the targets continuously for several days in order not to miss any transit. The runs are typically one to two weeks long, about three runs per year per cluster in two or three subsequent years for about ten clusters. There are thousands of stars detectable in each field with several hundred known cluster members, e.g. in the first cluster observed, Tr-37, a typical cluster for the YETI survey, there are at least 469 known young stars detected in YETI data down to R=16.5 mag with sufficient precision of 50 milli-mag rms (5 mmag rms down to R=14.5 mag) to detect transits, so that we can expect at least about one young transiting object in this cluster. If we observe 10 similar clusters, we can expect to detect approximately 10 young transiting planets with radius determinations. The precision given above is for a typical telescope of the YETI network, namely the 60/90-cm Jena telescope (similar brightness limit, namely within +/-1 mag, for the others) so that planetary transits can be detected. For planets with mass and radius determinations, we can calculate the mean density and probe the internal structure. We aim to constrain planet formation models and their time-scales by discovering planets younger than 100 Myr and determining not only their orbital parameters, but also measuring their true masses and radii, which is possible so far only by the transit method. Here, we present an overview and first results. (Abstract shortened)Comment: 15 pages, 10 figures, AN accepted 2011 June 1

INPOP08, a 4-D planetary ephemeris: From asteroid and time-scale computations to ESA Mars Express and Venus Express contributions

The latest version of the planetary ephemerides developed at the Paris Observatory and at the Besancon Observatory is presented here. INPOP08 is a 4-dimension ephemeris since it provides to users positions and velocities of planets and the relation between TT and TDB. Investigations leading to improve the modeling of asteroids are described as well as the new sets of observations used for the fit of INPOP08. New observations provided by the European Space Agency (ESA) deduced from the tracking of the Mars Express (MEX) and Venus Express (VEX) missions are presented as well as the normal point deduced from the Cassini mission. We show the huge impact brought by these observations in the fit of INPOP08, especially in terms of Venus, Saturn and Earth-Moon barycenter orbits.Comment: 14 pages. submitted to A&A. accepted in A&

Progress and Opportunities of Foundation Models in Bioinformatics

Bioinformatics has witnessed a paradigm shift with the increasing integration of artificial intelligence (AI), particularly through the adoption of foundation models (FMs). These AI techniques have rapidly advanced, addressing historical challenges in bioinformatics such as the scarcity of annotated data and the presence of data noise. FMs are particularly adept at handling large-scale, unlabeled data, a common scenario in biological contexts due to the time-consuming and costly nature of experimentally determining labeled data. This characteristic has allowed FMs to excel and achieve notable results in various downstream validation tasks, demonstrating their ability to represent diverse biological entities effectively. Undoubtedly, FMs have ushered in a new era in computational biology, especially in the realm of deep learning. The primary goal of this survey is to conduct a systematic investigation and summary of FMs in bioinformatics, tracing their evolution, current research status, and the methodologies employed. Central to our focus is the application of FMs to specific biological problems, aiming to guide the research community in choosing appropriate FMs for their research needs. We delve into the specifics of the problem at hand including sequence analysis, structure prediction, function annotation, and multimodal integration, comparing the structures and advancements against traditional methods. Furthermore, the review analyses challenges and limitations faced by FMs in biology, such as data noise, model explainability, and potential biases. Finally, we outline potential development paths and strategies for FMs in future biological research, setting the stage for continued innovation and application in this rapidly evolving field. This comprehensive review serves not only as an academic resource but also as a roadmap for future explorations and applications of FMs in biology.Comment: 27 pages, 3 figures, 2 table

Polycyclic aromatic hydrocarbon processing in interstellar shocks

Context: PAHs appear to be an ubiquitous interstellar dust component but the effects of shocks waves upon them have never been fully investigated. Aims: To study the effects of energetic (~0.01-1 keV) ion (H, He and C) and electron collisions on PAHs in interstellar shock waves.Methods: We calculate the ion-PAH and electron-PAH nuclear and electronic interactions, above the threshold for carbon atom loss from a PAH, in 50-200 km/s shock waves in the warm intercloud medium. Results: Interstellar PAHs (Nc = 50) do not survive in shocks with velocities greater than 100 km/s and larger PAHs (Nc = 200) are destroyed for shocks with velocities greater/equal to 125 km/s. For shocks in the ~75 - 100 km/s range, where destruction is not complete, the PAH structure is likely to be severely denatured by the loss of an important fraction (20-40%) of the carbon atoms. We derive typical PAH lifetimes of the order of a few x10^8 yr for the Galaxy. These results are robust and independent of the uncertainties in some key parameters that have yet to be well-determined experimentally. Conclusions: The observation of PAH emission in shock regions implies that that emission either arises outside the shocked region or that those regions entrain denser clumps that, unless they are completely ablated and eroded in the shocked gas, allow dust and PAHs to survive in extreme environments.Comment: 19 pages, 11 figures, 3 tables, typos corrected and PAH acronym in the title substituted with full name to match version published in Astronomy and Astrophysic

Nanoscale integration of single cell biologics discovery processes using optofluidic manipulation and monitoring.

The new and rapid advancement in the complexity of biologics drug discovery has been driven by a deeper understanding of biological systems combined with innovative new therapeutic modalities, paving the way to breakthrough therapies for previously intractable diseases. These exciting times in biomedical innovation require the development of novel technologies to facilitate the sophisticated, multifaceted, high-paced workflows necessary to support modern large molecule drug discovery. A high-level aspiration is a true integration of "lab-on-a-chip" methods that vastly miniaturize cellulmical experiments could transform the speed, cost, and success of multiple workstreams in biologics development. Several microscale bioprocess technologies have been established that incrementally address these needs, yet each is inflexibly designed for a very specific process thus limiting an integrated holistic application. A more fully integrated nanoscale approach that incorporates manipulation, culture, analytics, and traceable digital record keeping of thousands of single cells in a relevant nanoenvironment would be a transformative technology capable of keeping pace with today's rapid and complex drug discovery demands. The recent advent of optical manipulation of cells using light-induced electrokinetics with micro- and nanoscale cell culture is poised to revolutionize both fundamental and applied biological research. In this review, we summarize the current state of the art for optical manipulation techniques and discuss emerging biological applications of this technology. In particular, we focus on promising prospects for drug discovery workflows, including antibody discovery, bioassay development, antibody engineering, and cell line development, which are enabled by the automation and industrialization of an integrated optoelectronic single-cell manipulation and culture platform. Continued development of such platforms will be well positioned to overcome many of the challenges currently associated with fragmented, low-throughput bioprocess workflows in biopharma and life science research

Community-Based Provision of Statin and Aspirin After the Detection of Coronary Artery Calcium Within a Community-Based Screening Cohort

ObjectivesWe examined the association of coronary artery calcium (CAC) detected on a screening exam with subsequent statin and aspirin usage in a healthy male screening cohort.BackgroundWhether the presence of CAC, an independent predictor of coronary heart disease outcomes, alters clinical management, such as the use of preventive medications, is unknown.MethodsMen (n = 1,640) ages 40 to 50 years (mean 42 years) were screened for coronary heart disease risk factors and CAC. The CAC scores and risk factors were reported to patients, and results were made available in the electronic medical record; however, medications were not prescribed or recommended by the study. During up to 6 years of subsequent annual structured telephone follow-up, we observed the community-based initiation and persistence of aspirin and statin therapy.ResultsA progressive increase in the incidence of pharmacotherapy was noted over time such that those with CAC were 3 times more likely to receive a statin (48.5% vs. 15.5%, p < 0.001) and also significantly more likely to receive aspirin (53.0% vs. 32.3%; p < 0.001) than those without CAC. In multivariable models controlling for National Cholesterol Education Program risk variables and baseline medication use, CAC was strongly and independently associated with use of either statin (odds ratio [OR] 3.53; 95% confidence interval [CI] 2.66 to 4.69), aspirin (OR 3.05; 95% CI 2.30 to 4.05) or both (OR 6.97; 95% CI 4.81 to 10.10).ConclusionsIn this prospective cohort, the presence of coronary calcification was associated with an independent 3-fold greater likelihood of statin and aspirin usage