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Structure-switching aptamers have become ubiquitous in several applications, notably in analytical devices such as biosensors, due to their ease of supporting strong signaling. Aside from their ability to bind specifically with their respective target, this class of aptamers also undergoes a conformational rearrangement upon target recognition. While several well-studied and early-developed aptamers (e.g., cocaine, ATP, and thrombin) have been found to have this structure-switching property, the vast majority do not. As a result, it is common to try to engineer aptamers into switches. This proves challenging in part because of the difficulty in obtaining structural and functional information about aptamers. In response, we review various readily available biophysical characterization tools that are capable of assessing structure switching of aptamers. In doing so, we delve into the fundamentals of these different techniques and detail how they have been utilized in characterizing structure-switching aptamers. While each of these biophysical techniques alone has utility, their real power to demonstrate the occurrence of structural change with ligand binding is when multiple techniques are used. We hope that through a deeper understanding of these techniques, researchers will be better able to acquire biophysical information about their aptamer–ligand systems and accelerate the translation of aptamers into biosensors.
This paper proves normalisation theorems for intuitionist and classical negative free logic, without and with the operator for definite descriptions. Rules specific to free logic give rise to new kinds of maximal formulas additional to those familiar from standard intuitionist and classical logic. When is added it must be ensured that reduction procedures involving replacements of parameters by terms do not introduce new maximal formulas of higher degree than the ones removed. The problem is solved by a rule that permits restricting these terms in the rules for $\forall $, $\exists $ and to parameters or constants. A restricted subformula property for deductions in systems without is considered. It is improved upon by an alternative formalisation of free logic building on an idea of Jaśkowski’s. In the classical system the rules for require treatment known from normalisation for classical logic with $\lor $ or $\exists $. The philosophical significance of the results is also indicated.
We propose a method for cutting down a random recursive tree that focuses on its higher-degree vertices. Enumerate the vertices of a random recursive tree of size n according to the decreasing order of their degrees; namely, let $(v^{(i)})_{i=1}^{n}$ be such that $\deg(v^{(1)}) \geq \cdots \geq \deg (v^{(n)})$. The targeted vertex-cutting process is performed by sequentially removing vertices $v^{(1)}, v^{(2)}, \ldots, v^{(n)}$ and keeping only the subtree containing the root after each removal. The algorithm ends when the root is picked to be removed. The total number of steps for this procedure, $K_n$, is upper bounded by $Z_{\geq D}$, which denotes the number of vertices that have degree at least as large as the degree of the root. We prove that $\ln Z_{\geq D}$ grows as $\ln n$ asymptotically and obtain its limiting behavior in probability. Moreover, we obtain that the kth moment of $\ln Z_{\geq D}$ is proportional to $(\!\ln n)^k$. As a consequence, we obtain that the first-order growth of $K_n$ is upper bounded by $n^{1-\ln 2}$, which is substantially smaller than the required number of removals if, instead, the vertices were selected uniformly at random.
Safe vaccines are critical for biosecurity protection, yet adverse events—rightly or wrongly attributed to immunization—potentially cause rapid loss of confidence, reduced vaccine uptake, and resurgence of preventable disease. Effective vaccine safety incident management is essential to provide assessment and lead appropriate actions to ensure vaccination programs are safe and mitigate unwarranted crisis escalation that could damage vaccine programs and the effective control of vaccine preventable disease outbreaks or pandemics. Incident management systems (IMS) are used globally to direct emergency management response, particularly for natural disasters of fire, flood, and storm. Public health is equally an emergency response and can therefore benefit from these command control constructs. While examples of IMS for outbreak response and mass immunization logistics exist, there is little to no information on their use in vaccine safety. We describe Australia’s vaccine safety Alert Advisory Group establishment in Victoria during the COVID-19 pandemic and onward embedding into routine practice, anticipant of new vaccines, and the next biosecurity threat.
Amoxicillin suspension is frequently prescribed to children; we hypothesized that prescribing convention system constraints lead to unusual dosing regimens and unnecessary waste of the drug.
Objective:
Identify antibiotic dispensing practices by community pharmacists and/or technicians to understand opportunities to decrease wasted amoxicillin liquid and optimize prescribing convention of liquid amoxicillin to children.
Methods:
Pilot online survey of Atlanta area and National Community Pharmacists Association pharmacists or pharmacy technicians that self-reported dispensing amoxicillin suspension. Questions regarding liquid amoxicillin dispensing practices and other open comments were asked about suggestions to decrease amoxicillin waste from March 13 to April 5, 2023.
Results:
Among 68 pharmacy staff that participated, over 90% reported dispensing extra liquid amoxicillin to patients for more than 10% of the doses they dispensed. Twenty-seven respondents (39.7%) felt that amoxicillin waste was a problem; waste was most often due to package/bottle sizing issues (n = 64 of 67 responses, 95.5%). Respondents reported instructing families to dispose of extra medication in the trash (n = 51, 75%); 11 (16.2%) instructed pour the remaining in the sink; none reported requesting return to the pharmacy, and 6 (8.8%) reported other instructions. Community pharmacists observed that computerized algorithms create odd dosing amounts and that some prescribers add to the overall amount needed routinely.
Conclusion:
Community pharmacists in this pilot survey observed prescribing conventions, manufacturing, regulatory, and electronic medical record constraints that lead to liquid amoxicillin waste or confusing amounts for families to use.
The Scottish Small Isles – comprising Muck, Rùm, Eigg, Canna, and by extension, Coll – are geologically complex, with intersecting rock samples from the Archean (Lewisian Gneiss basements formed approximately 3 billion years ago), Proterozoic (Torridonian sandstone formed approximately 1 billion years ago), Mesozoic (sedimentation deposited approximately 200 million years ago) and Palaeocene (basalt formed approximately 55.8 million years ago as part of the Palaeocene–Eocene Thermal Maximum event). This practice research article – drawing on palaeontology, kinaesthetic learning and creative writing – takes the Small Isles as a case study for what geologist Marcia Bjornerud defines as a discernible “timefulness” that humans should seek to attain: “an acute consciousness of how the world is made by–indeed, made of–time” (2020, Timefulness: How Thinking Like a Geologist Can Help Save the World, 5). Through their lithic intrusions, and interruptive strata, the Small Isles offer an alternative form of pedagogy: where multiple epochs, tenses and tempos visibly converse with one another; where “polytemporality” can be witnessed and physically experienced; where the notion of linear time is destabilised.
The Australian debate over Investor-State Dispute Settlement (ISDS) sharpened in 2023 because Australian mining billionaire Clive Palmer, having previously registered his mining company in Singapore, has claimed to be a Singaporean investor. He is using ISDS provisions in the 2012 ASEAN-Australia-New Zealand Free Trade Agreement and the amended 2017 Singapore-Australia Free Trade Agreement to sue the Australian government for a total of A$410 billion in three separate claims. This article uses Cox’s critical theory framework developed by Schneiderman to explain the historical development and power dynamics of ISDS, the contest between its business supporters and social movement critics, and the impact of this contest on governments. It then analyses the Palmer claims and explores the global debate about ISDS, including its increased use by fossil fuel companies against government regulation of carbon emissions, which has led to increased resistance from social movements and governments. ISDS is also being reviewed by the United Nations and World Bank institutions which provide arbitrators for its tribunals and by the Organisation for Economic Co-operation and Development. The conclusion assesses the debate over whether ISDS can be reformed and its future viability.
We present and study a novel algorithm for the computation of 2-Wasserstein population barycenters of absolutely continuous probability measures on Euclidean space. The proposed method can be seen as a stochastic gradient descent procedure in the 2-Wasserstein space, as well as a manifestation of a law of large numbers therein. The algorithm aims to find a Karcher mean or critical point in this setting, and can be implemented ‘online’, sequentially using independent and identically distributed random measures sampled from the population law. We provide natural sufficient conditions for this algorithm to almost surely converge in the Wasserstein space towards the population barycenter, and we introduce a novel, general condition which ensures uniqueness of Karcher means and, moreover, allows us to obtain explicit, parametric convergence rates for the expected optimality gap. We also study the mini-batch version of this algorithm, and discuss examples of families of population laws to which our method and results can be applied. This work expands and deepens ideas and results introduced in an early version of Backhoff-Veraguas et al. (2022), in which a statistical application (and numerical implementation) of this method is developed in the context of Bayesian learning.
Companies and business lobby groups bemoan a lack of qualified workers, even for entry-level or low-skill jobs. At issue is a stated inability to find workers with the right ‘fit’ for the role or business. But what does fit really mean? We draw on human capital theory and labour segmentation theory to examine how perceptions of fit are shaped. We conducted ninety-three interviews with food service workers, managers, and other industry stakeholders and found that employment decisions are shaped by stereotypes, with a particular focus on ‘pretty privilege’ or aesthetic labour, as well as Indigeneity, citizenship, race, and gender. We present implications for research and practice in the food services industry.
The Women, Peace, and Security (WPS) sector assumes increasing the number of women involved in peace negotiations drives better outcomes for local women. However, empirical support for this assumption is inconsistent. This article tests how power alters the relationship between women’s formal (Track 1) involvement in peace negotiations and the inclusion of women-specific provisions in peace agreements. Using an original dataset comprised of 2,299 Track 1 delegates involved in 116 comprehensive peace agreements finalized between 1990 and 2021, I find women’s involvement in peace negotiations is positively correlated to comprehensive agreements containing provisions for women. However, this correlation is dependent on women holding positions of power—simply having women in the room is insufficient. This article offers a novel quantitative approach to WPS studies, provides nuance to theories linking descriptive and substantive representation, and casts doubt on the longstanding assumption that increasing women’s involvement inherently enhances gender equality.
Two doctrines (or axioms) of christian theology sharply distinguish christian monotheism from its traditional monotheistic siblings (viz. jewish and islamic monotheism): the incarnation of God and the triunity of God. Both doctrines, as many have long observed, face a conspicuous so-called logical problem – namely, apparent contradiction. How should the strong appearance of such fundamental contradiction be explained? Beall's answer: the incarnation and trinity appear to be contradictory because God is a contradictory being – a being of whom some contradictions are true. The full truth of God is expressed only via contradiction, which is why the fundamental axioms of christian theology have long appeared to be contradictory. Divine Contradiction presents the target contradictory account of the trinity; its predecessor The Contradictory Christ presents the contradictory account of the incarnation.
This study addresses the importance of orofacial gestures and acoustic cues to execute prosodic patterns under different communicative settings in Farsi. Given that Farsi lacks morpho-syntactic markers for polar questions, we aim to determine whether specific facial movements accompany the prosodic correlates of questionhood in Farsi under conditions of degraded information, that is, whispering and wearing face masks. We hypothesise speakers will employ the most pronounced facial expressions when whispering questions with a face mask to compensate for the absence of F0, reduced intensity and lower face invisibility. To this end, we conducted an experiment with 10 Persian speakers producing 10 pairs of statements and questions in normal and whispered speech modes with and without face masks. Our results provide support to our hypotheses that speakers will intensify their orofacial expressions when confronted with marked conditions. We interpreted our results in terms of the ‘hand in hand’ and ‘trade-off’ hypothesis. In whispered speech, the parallel realisation of longer word duration and orofacial expressions may be a compensatory mechanism for the limited options to convey intonation. Also, the lower face coverage is mutually compensated for by word duration and intensified upper facial expressions, all of which in turn support the trade-off hypothesis.
We consider the estimation of rare-event probabilities using sample proportions output by naive Monte Carlo or collected data. Unlike using variance reduction techniques, this naive estimator does not have an a priori relative efficiency guarantee. On the other hand, due to the recent surge of sophisticated rare-event problems arising in safety evaluations of intelligent systems, efficiency-guaranteed variance reduction may face implementation challenges which, coupled with the availability of computation or data collection power, motivate the use of such a naive estimator. In this paper we study the uncertainty quantification, namely the construction, coverage validity, and tightness of confidence intervals, for rare-event probabilities using only sample proportions. In addition to the known normality, Wilson, and exact intervals, we investigate and compare them with two new intervals derived from Chernoff’s inequality and the Berry–Esseen theorem. Moreover, we generalize our results to the natural situation where sampling stops by reaching a target number of rare-event hits. Our findings show that the normality and Wilson intervals are not always valid, but they are close to the newly developed valid intervals in terms of half-width. In contrast, the exact interval is conservative, but safely guarantees the attainment of the nominal confidence level. Our new intervals, while being more conservative than the exact interval, provide useful insights into understanding the tightness of the considered intervals.
The fern of Achala Asplenium achalense Hieron. (Aspleniaceae), endemic to north-west and central Argentina, was formerly considered a lost species. We describe its rediscovery in August 2022 in the Yungas biogeographical province, compile a map of all historical and current records of the species, and propose an IUCN Red List status. We estimated the fern of Achala's range using the area of occupancy of the rediscovered population, calculated as 4 km2 because it is located in a single 2 × 2 km grid square. The extent of occurrence cannot be calculated because only a single living population is known. These data suggest a provisional categorization of the fern of Achala as Critically Endangered based on criteria B2ab(i,ii,iii,iv,v). The species should be considered Regionally Extinct in its locus classicus in Comechingones biogeographical province. We recommend securing the conservation of the single known population (which does not lie within a conservation unit), further surveys for the species in the five protected areas where it was recorded historically, and restoration of the species in the wild. To support the latter, we are cultivating spores and gametophytes of the fern of Achala, in collaboration with colleagues from the National University of La Plata.
Critics point to increasing private lawsuits filed by students accused of campus sexual assault as evidence that Obama-era Title IX guidance overcorrected and favored victims at the expense of the due process rights of the accused. This overcorrection narrative powerfully reshaped the debate surrounding campus sexual assault and ultimately contributed to the rescinding of the guidance. Existing analytical tools from legal mobilization scholarship – emphasizing the deployment of litigation by social movement actors – are not equipped to identify the origins and dissemination of this political narrative. Drawing from legal complaints, media coverage and interviews with lawyers, we show how private practice attorneys with no visible movement ties helped craft the overcorrection narrative from individual lawsuits by (1) embedding political claims in legal filings, (2) amplifying the narrative in media and (3) collaborating with advocates in quantifying the litigation trend. We extend prior scholarship and illustrate how lawsuits can be both a vehicle of political storytelling and the story itself. We further argue that the ideology of liberal legalism can mask the politics of private lawsuits, making litigation a useful tool for social movement efforts to mobilize support for legal reform.