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Background: Antibiotics are frequently prescribed–and overprescribed–at hospital discharge, leading to adverse-events and patient harm. Our understanding of how to optimize prescribing at discharge is limited. Recently, we published the ROAD (Reducing Overuse of Antibiotics at Discharge) Home Framework, which identified potential strategies to improve antibiotic prescribing at discharge across 3 tiers: Tier 1–Critical infrastructure, Tier 2–Broad inpatient interventions, Tier 3–Discharge-specific strategies. Here, we used the ROAD Home Framework to assess the association of stewardship strategies with antibiotic overuse at discharge and to describe pathways toward improved discharge prescribing. Methods: In fall 2019, we surveyed 39 Michigan hospitals on their antibiotic stewardship strategies. For patients hospitalized at participating hospitals July 1, 2017, through July 30, 2019, and treated for community-acquired pneumonia (CAP) and urinary tract infection (UTI), we assessed the association of reported strategies with days of antibiotic overuse at discharge. Days of antibiotic overuse at discharge were defined based on national guidelines and included unnecessary therapy, excess duration, and suboptimal fluoroquinolone use. We evaluated the association of stewardship strategies with days of discharge antibiotic overuse 2 ways: (1) all stewardship strategies were assumed to have equal weight, and (2) strategies weighted using the ROAD Home Framework with tier 3 (discharge-specific) strategies had the highest weight. Results: Overall, 39 hospitals with 20,444 patients (56.5% CAP; 43.5% UTI) were included. The survey response rate was 100% (39 of 39). Hospitals reported a median of 12 (IQR, 9–14) of 33 possible stewardship strategies (Fig. 1). On bivariable analyses, review of antibiotics prior to discharge was the only strategy consistently associated with lower antibiotic overuse at discharge (aIRR, 0.543; 95% CI, 0.335–0.878). On multivariable analysis, weighting by ROAD Home tier predicted antibiotic overuse at discharge for both CAP and UTI. For diseases combined, having more weighted strategies was associated with lower antibiotic overuse at discharge (aIRR per weighted intervention, 0.957; 95% CI, 0.927–0.987). Discharge-specific stewardship strategies were associated with a 12.4% relative decrease in antibiotic overuse days at discharge. Based on these findings, 3 pathways emerged to improve antibiotic use at discharge (Fig. 2): inpatient-focused strategies, “doing it all,” and discharge-focused strategies. Conclusions: The more stewardship strategies reported, the lower a hospitals’ antibiotic overuse at discharge. However, different pathways to improve discharge antibiotic use exist. Thus, discharge stewardship strategies should be tailored. Specifically, hospitals with limited stewardship resources and infrastructure should consider implementing a discharge-specific strategy straightaway. In contrast, hospitals that already have substantial inpatient infrastructure may benefit from proactively incorporating discharge into their existing strategies.
Changes in antimicrobial use during the pandemic in relation to long-term trends in utilization among different antimicrobial stewardship program models have not been fully characterized. We analyzed data from an integrated health system using joinpoint regression and found temporal fluctuations in prescribing as well as continuation of existing trends.
We describe the scientific goals and survey design of the First Large Absorption Survey in H i (FLASH), a wide field survey for 21-cm line absorption in neutral atomic hydrogen (H i) at intermediate cosmological redshifts. FLASH will be carried out with the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope and is planned to cover the sky south of
$\delta \approx +40\,\deg$
at frequencies between 711.5 and 999.5 MHz. At redshifts between
$z = 0.4$
and
$1.0$
(look-back times of 4 – 8 Gyr), the H i content of the Universe has been poorly explored due to the difficulty of carrying out radio surveys for faint 21-cm line emission and, at ultra-violet wavelengths, space-borne searches for Damped Lyman-
$\alpha$
absorption in quasar spectra. The ASKAP wide field of view and large spectral bandwidth, in combination with a radio-quiet site, will enable a search for absorption lines in the radio spectra of bright continuum sources over 80% of the sky. This survey is expected to detect at least several hundred intervening 21-cm absorbers and will produce an H i-absorption-selected catalogue of galaxies rich in cool, star-forming gas, some of which may be concealed from optical surveys. Likewise, at least several hundred associated 21-cm absorbers are expected to be detected within the host galaxies of radio sources at
$0.4 < z < 1.0$
, providing valuable kinematical information for models of gas accretion and jet-driven feedback in radio-loud active galactic nuclei. FLASH will also detect OH 18-cm absorbers in diffuse molecular gas, megamaser OH emission, radio recombination lines, and stacked H i emission.
We present the most sensitive and detailed view of the neutral hydrogen (
${\rm H\small I}$
) emission associated with the Small Magellanic Cloud (SMC), through the combination of data from the Australian Square Kilometre Array Pathfinder (ASKAP) and Parkes (Murriyang), as part of the Galactic Australian Square Kilometre Array Pathfinder (GASKAP) pilot survey. These GASKAP-HI pilot observations, for the first time, reveal
${\rm H\small I}$
in the SMC on similar physical scales as other important tracers of the interstellar medium, such as molecular gas and dust. The resultant image cube possesses an rms noise level of 1.1 K (
$1.6\,\mathrm{mJy\ beam}^{-1}$
)
$\mathrm{per}\ 0.98\,\mathrm{km\ s}^{-1}$
spectral channel with an angular resolution of
$30^{\prime\prime}$
(
${\sim}10\,\mathrm{pc}$
). We discuss the calibration scheme and the custom imaging pipeline that utilises a joint deconvolution approach, efficiently distributed across a computing cluster, to accurately recover the emission extending across the entire
${\sim}25\,\mathrm{deg}^2$
field-of-view. We provide an overview of the data products and characterise several aspects including the noise properties as a function of angular resolution and the represented spatial scales by deriving the global transfer function over the full spectral range. A preliminary spatial power spectrum analysis on individual spectral channels reveals that the power law nature of the density distribution extends down to scales of 10 pc. We highlight the scientific potential of these data by comparing the properties of an outflowing high-velocity cloud with previous ASKAP+Parkes
${\rm H\small I}$
test observations.
The essay takes a non-Eurocentric point of view and aims to highlight the concurrent concepts of piracy and other forms of maritime violence in the early modern Mediterranean. The author shows that a wide range of concepts were used in the early modern Ottoman Empire to conceptualize what Europeans termed piracy or privateering. As in Europe, there was considerable ambiguity in the use and interpretation of these terms, and the practices that they described. In contrast to the emphasis that contemporary Europeans put on the distinction between piracy and privateering, in theory if not always in practice, Ottoman Islamic law did not differentiate between foreign Christian pirates and foreign Christian corsairs or privateers.
“Think of jihad as an island,” wrote the sixteenth-century Ottoman bureaucrat, historian, and social commentator Mustafa Ali: “On its right is a sea of wealth, on the left is corruption.” Corsairing and piracy, holy war and criminal rebellion – the opposing legal poles of Mediterranean maritime raiding were not distinguished by tactics, equipment, or even personnel, but by targeting and authorization, or its absence. Mustafa Ali argued that many of the holy warrior heroes (gazis, in Ottoman parlance) who had brought North Africa into the Ottoman fold, corsairs like Hayreddin Barbarossa (d. 1546) and Turgud Reis (d. 1565), had begun their careers as petty coastal pirates, preying on Christian and Muslim Ottomans in the Aegean. With time and success, they expanded their operations, improved the size and range of their craft, and only then transitioned to legitimate corsairing in service of the faith and the sultan. By repenting of their earlier sins and devoting themselves to maritime jihad against the enemies of Islam and the Ottoman dynasty, however, these corsairs earned their place in the Ottoman pantheon and their reward in the hereafter.
But, writing just before his death in 1600, Mustafa Ali observed that over the past generation it had become increasingly difficult to distinguish between the small-time pirates then following similar career paths along the Adriatic and Aegean coasts and the North Africa-bound corsairs they may have aspired to become.
The Rapid ASKAP Continuum Survey (RACS) is the first large sky survey using the Australian Square Kilometre Array Pathfinder (ASKAP), covering the sky south of
$+41^\circ$
declination. With ASKAP’s large, instantaneous field of view,
${\sim}31\,\mathrm{deg}^2$
, RACS observed the entire sky at a central frequency of 887.5 MHz using 903 individual pointings with 15 minute observations. This has resulted in the deepest radio survey of the full Southern sky to date at these frequencies. In this paper, we present the first Stokes I catalogue derived from the RACS survey. This catalogue was assembled from 799 tiles that could be convolved to a common resolution of
$25^{\prime\prime}$
, covering a large contiguous region in the declination range
$\delta=-80^{\circ}$
to
$+30^\circ$
. The catalogue provides an important tool for both the preparation of future ASKAP surveys and for scientific research. It consists of
$\sim$
2.1 million sources and excludes the
$|b|<5^{\circ}$
region around the Galactic plane. This provides a first extragalactic catalogue with ASKAP covering the majority of the sky (
$\delta<+30^{\circ}$
). We describe the methods to obtain this catalogue from the initial RACS observations and discuss the verification of the data, to highlight its quality. Using simulations, we find this catalogue detects 95% of point sources at an integrated flux density of
$\sim$
5 mJy. Assuming a typical sky source distribution model, this suggests an overall 95% point source completeness at an integrated flux density
$\sim$
3 mJy. The catalogue will be available through the CSIRO ASKAP Science Data Archive (CASDA).
Dietary patterns high in fat contribute to the onset of cardiometabolic disease through the accrual of adipose tissue (AT). Lycopene, a carotenoid shown to exert multiple health benefits, may disrupt these metabolic perturbations. The purpose of the present study was to evaluate AT development and obesity-associated metabolic outcomes in the neonate and weanling offspring of Sprague-Dawley mothers fed a high-fat diet (HFD = 50 % fat) with and without lycopene supplementation. Sprague-Dawley rats consumed either a normal fat diet (NFD; 25 % fat) or HFD throughout gestation. Upon delivery, half of HFD mothers were transitioned to an HFD supplemented with 1 % lycopene (HFDL). At postnatal day 14 (P14), P25, and P35, pups were euthanised, body weight was recorded, and visceral white AT (WAT) and brown AT (BAT) mass were determined. Serum redox status, adipokines, glucose and inflammatory biomarkers were evaluated, as well as BAT mRNA expression of uncoupling protein 1 (UCP1). The HFD was effective in inducing weight gain as evident by significantly greater BW and WAT in the HFD group compared to the NFD group across all time points. Compared to HFD, the HFDL group exhibited significantly greater BAT with concomitant reductions in WAT mass, serum lipid peroxides and serum glucose. No significant differences were observed in serum adipokines, inflammatory markers or UCP1 expression despite the aforementioned alterations in AT development. Results suggest that dietary lycopene supplementation may influence metabolic outcomes during the weaning and post-weaning periods. Additional research is warranted to elucidate molecular mechanisms by which lycopene influences AT biology.
From the very outset Darwin’s extensive use of metaphor in the Origin has proved controversial, with some people thinking Darwin was thereby committed to ascribing intentions or even consciousness to nature, and others fearing that readers would be misled into thinking that he was. Also, some have argued (e.g. Gillian Beer) that Darwin should be regarded as much as a poet as a scientist. We argue that, on the contrary, his metaphors have a substantively scientific role, and do real work in the development of his argument. Firstly, as Darwin himself stresses, ‘such metaphorical expressions… are almost necessary for brevity’. Secondly, they provide a method for forming new concepts (as in the case of ‘struggle’). Thirdly, and, most significantly, the use of metaphor enables Darwin to explore further the analogy between NS and AS and directly compare the achievements of human breeding and those of the struggle for existence.
Our task here is to address four authors who have given different accounts of Darwin’s argument from ours: Richard A. Richards; Peter Gildenhuys; James Lennox; and D. Graham Burnett. Viewing analogical argumentation as hopelessly unclassy, each has sought to save Darwin’s reputation by denying that he founded his theory of natural selection on an analogical argument, and by offering alternative, non-analogical readings of Darwin’s argumentation. For Lennox, Darwin met the adequacy requirement of the vera causa tradition not through analogy but through speculative conjectures: “Darwinian thought experiments,” Lennox calls them. For Richards, the Origin should be read as an experimental report, in which artificial selection is the cause of new domesticated varieties that periodically go feral, allowing us, as the varieties return to the wild state, to observe the effects of natural selection in action. Explaining why these revisionist accounts cannot be accepted will confirm our explicit views about analogical argumentation, and some implicit ones about relating texts and contexts.
The concept of analogy was first analysed in classical Greek thought. By 'analogy' was meant a four-term relation: A is to B as C is to D. Initially, within Greek mathematics, analogy expressed the equality of the relative magnitudes of two line pairs, when the ratio of line A to line B is identical with the ratio of line C to line D. An analogy asserted a proportionality. And the theory of similar triangles exhibits the basic form of argument by analogy, with a set of valid proofs showing which additional properties, equiangularity say, the two triangles must share. In Euclid are all the features of the analogical relationship relevant to our enquiry. For analogy was soon taken beyond its mathematical confines, especially by Aristotle, in exploring how these geometrical concepts can be applied in empirical contexts. These explorations kept the commitment to proportionality, which persists in every modern analyst of analogy knowingly upholding the Aristotelian tradition.
Central to this book is a trio of chapters (4, 5 and 6) on Darwin’s Origin of Species in its first edition of 1859. Darwin called his book 'one long argument'. These three chapters clarify how this long argument is conducted; how Darwin’s analogical reasonings about natural and artificial selection support the argument; and how his various metaphors are grounded in those reasonings. The conclusions from these chapters support the claims in our chapters 1 to 3 about the decisive antecedents, from ancient times on, for Darwin’s conception of analogical reasoning and what it can do for his one long argument. Equally these conclusions support the claims made in our chapters 7and 8 as to how that reasoning should be analysed and evaluated by philosophers, biologists and historians today. Our writing combines throughout narratives that are often not overtly normative with judgements that often are so.
In the decades before the Origin, a split arises between two very different concepts of analogy, and so two views of argument by analogy. Some people, taking 'analogy' as a synonym for 'similarity',came to a new understanding of 'argument by analogy': suppose A and B are known to share a number of properties, then the probability is increased that B also possesses some other property which A is known to possess. This account remains widely assumed even today. Other people, largely within Anglican theology and concerned with the analogy between God and the world, insisted that the only correct use of the word 'analogy' was in its original Greek sense, including the Aristotelian commitment to proportionality, and so to relational comparisons, as when God is related to his creatures as a human father is to his children. This commitment grounded a view radically different from the new similarity view. In analysing what an argument by analogy is, Richard Whately, and following him J. S. Mill, specified explicitly the conditions for such an argument to be valid. It is this account that is relevant to an understanding of Darwin’s use of analogy.
This chapter engages two clusters of long-run, big-picture issues. One concerns relations between art and nature. Aristotle’s views on this were challenged in the late seventeenth century by Robert Boyle in defending the new mechanical philosophy. Darwin is aligned with neither Aristotle nor Boyle; nor with German Romantic philosophers, such as Schelling. The agrarian contexts of Darwin’s science, and its alignments with agrarian rather than industrial forms of capitalism, illuminate Darwin’s views, including his natural theological views, of art-nature relations. A second cluster of issues concerns the role of the selection analogy in later controversies about natural selection, notably involving Alfred Russel Wallace and Francis Galton in the nineteenth century, and Ronald Fisher and Sewall Wright in the twentieth century. We stress that Darwin’s theorising is sometimes ancient in its resources and sometimes modern, which is not surprising given the intellectual life he was leading. His analogical argument belongs in the science classroom not because it is up-to-date but precisely because, like all science, it is of its time.
Against this background, we turn to Darwin himself. We first look at the selection analogy in his theorising before writing the Origin. Darwin arrived at his theory of natural selection before contemplating such an analogy. We cannot, then, understand the analogy as what led him to the theory. Its role was to support a theory already arrived at. The evolutionary process takes place over millions of years at an imperceptibly slow pace, and so is inaccessible to direct observation. However, here and now we can observe the selective human breeding of domestic animals and cultivated plants. Darwin can then use an argument by analogy to give his theory indirect empirical support. The struggle for existence in the wild and the human breeders are not intrinsically similar agencies, but are relationally comparable in having the same kind of causal relation to the animals and plants that they are acting on with effects similar in kind but not in degree.
There are conditions satisfied by successful analogical arguments which Darwin’s argument satisfies. Darwin first establishes that breeding practices are an analogical model of the struggle for existence in the wild: just as humans discriminate in favour of animals and plants with desirable traits, so the struggle for existence discriminates in favour of creatures with traits best enabling them to cope with that struggle. Domestic breeding creates new varieties because it is systematic – there will be a tendency always to discriminate in favour of the same set of traits. The struggle for existence will have the same systematic tendency to favour certain traits at the expense of others. Therefore it is possible for it also to create new varieties. Darwin now alternates the analogy and its proportionality: if natural selection (NS) is to new wild varieties as artificial selection (AS) is to new domesticated varieties, then NS is to AS as new wild varieties are to new domesticated varieties. Thus if NS is a massively more efficient selector than AS, and the greater the cause, the greater the effect, then, a fortiori, NS should produce not only new varieties but new species.