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Recruitment and retention of populations with limited prior participation in clinical trials remains a challenge. Thus, an increased understanding of the complex factors that impede or facilitate recruitment and retention is needed. Adapting the Systems Engineering Initiative for Patient Safety (SEIPS), we developed the Systems Engineering Initiative for Participant-Centric Research (SEIPR) framework that researchers can use to develop, implement, and evaluate interventions to increase trial participation.
Methods:
We performed a non-systematic literature review using the digital databases PubMed and Google Scholar to determine factors facilitating and impeding involvement of populations with limited prior participation in clinical trials. From this literature, we developed the SEIPR framework by applying it to the context of recruitment and retention.
Results:
We organized key obstacles and evidence-based solutions into five framework components: Person, Tasks and Tools, Technology, Physical Environment, and Organizational Conditions. Common obstacles included lack of awareness of active trials by participants and healthcare providers, patient’s distance from trial centers, lack of access to traditional advertising technology, and mistrust towards investigators, among others. Solutions included promotional strategies appropriate to the regional or social context, decentralizing trials, providing communication technology to participants, partnering with trusted members from the participant’s community and primary care team, using local connections and community centers, financial incentives, and transportation solutions.
Discussion:
The SEIPR framework presents a promising tool for investigators interested in increasing participant breadth in clinical trials. Future research is needed to explore real-world applications and assess its effectiveness in recruiting and retaining broad populations.
The hydrogen isotope composition of the mantle provides insight into the advection, melting and metasomatism of the mantle, and the Earth’s water cycle. Because of sampling challenges, most estimates for the hydrogen composition of the mantle have been derived from basaltic glasses rather than from direct samples of the mantle. We present the first direct measurement of D/H ratios in nominally anhydrous orthopyroxene and olivine inclusions hosted within diamonds. The diamond hosts were recovered from placer deposits in Guyana, South America. The diamond-hosted inclusions preserve a population with δD of –31 ± 59‰ (normalised to Vienna Standard Mean Ocean Water). This value is D-enriched relative to that expected for a homogeneous upper mantle and is similar to values measured for arc basalts. We introduce three explanations for the observed D-enrichment in the anhydrous silicate inclusions. The hydrogen isotopic composition of the mantle might simply be heterogeneous in space and/or time. The measured D-enrichment could instead preserve local heterogeneity produced by fluids genetically related to the crystallisation of the diamond hosts. Local and mantle-wide processes might also have operated in concert, and overprint each other. Diamond-hosted silicate inclusions preserve an underexplored record of Earth’s water cycle.
Researchers frequently deliver treatments through messages, as in many audit and get-out-the-vote (GOTV) experiments. These message-based experiments often hinge on intermediary variables—actions subjects must take to actually receive the treatment or control embedded in a message. Whether subjects open the message is a crucial intermediary step, which can serve as a condition for estimating downstream treatment effects or as an outcome of interest in its own right. Yet opens are often measured with error, most notably when some openers are misclassified as non-openers in email-based studies. We characterize the resulting bias, derive interpretable bounds on effects for well-defined subgroups, and provide sensitivity analyses for mismeasurement, thereby offering practical guidance for message-based experiments conducted through email and other communication technologies.
Theileria annulata causes tropical theileriosis in cattle, yet the molecular basis of host–parasite crosstalk across intracellular stages remains incompletely defined. We combined RNA sequencing and untargeted metabolomics to profile paired uninfected and infected bovine leukocytes (schizont stage) and erythrocytes (piroplasm stage), together with purified schizonts and piroplasms. Integrated analyses revealed pronounced, cell type-specific reprogramming. Infected leukocytes showed activation of immune signalling, amino acid metabolism and energy-producing pathways, consistent with leukocyte transformation, whereas infected erythrocytes preferentially engaged glutathione metabolism and redox homeostasis. Parasite stage comparisons uncovered extensive transcriptional and metabolic rewiring, including stage-biased expression of mitochondrial components, antioxidant systems and putative stage-regulated transcription factors. These coherent host–parasite adaptations likely facilitate parasite survival and persistence within distinct cellular niches. This work delineates a stage-resolved multi-omics landscape of T. annulata infection spanning host and parasite compartments and identifies signalling and metabolic pathways that merit functional validation as candidates for improved diagnostics and targeted interventions against bovine tropical theileriosis.
Palaeoparasitological studies provide valuable insights into the presence of parasites in human groups and their relationship with diverse lifestyles, health conditions, and cultural practices of past populations. Twenty-two human coprolite samples were analysed to evaluate human–parasite interactions and understand the ways of life and their relationship with the environment during the Late Archaic and Formative Periods at the Aragón-1 site (3300 BCE to 530 CE), Atacama Desert (northern Chile). Samples were prepared using the spontaneous sedimentation technique and analysed by optical microscopy. 48 023 eggs were found and identified exclusively as Dibothriocephalus/Adenocephalus sp., suggesting parasite infection through the consumption of undercooked fish during both the Late Archaic and Early Formative Periods. Our analysis reveals a close ecological interaction between this parasitic genus and the humans who inhabited the Aragón-1 site. The presence of this parasite decreases significantly toward the later Period, a phenomenon that could be explained by cultural and/or environmental factors. Culinary practices, care and prevention, and El Niño and La Niña phenomena may have influenced the human–parasite dynamics. This study contributes to a deeper understanding of the biocultural practices of the Aragón-1 individuals, highlighting their dietary habits based on marine resources and the mobility between inland and coastal areas required for the procurement of these products.
We develop a diagrammatic approach to the representation theory of the quantum symmetric pairs corresponding to orthosymplectic Lie superalgebras inside general linear Lie superalgebras. Our approach is based on the disoriented skein category, which we define as a module category over the framed HOMFLYPT skein category. The disoriented skein category admits full incarnation functors to the categories of modules over the iquantum enveloping algebras corresponding to the quantum symmetric pairs, and it can be viewed as an interpolating category for these categories of modules. We define an equivalence of module categories between the disoriented skein category and the iquantum Brauer category (also known as the q-Brauer category), after endowing the latter with the structure of a module category over the framed HOMFLYPT skein category. The disoriented skein category has some advantages over the iquantum Brauer category, possessing duality structure and allowing the incarnation functors to be strict morphisms of module categories. Finally, we construct explicit bases for the morphism spaces of the disoriented skein and iquantum Brauer categories.
Whatever may have been thought in the past, including within the United Nations (UN), there is now no reason to doubt the status of the International Criminal Police Organization (INTERPOL) as an international organization.1 That is important for many reasons, including its status under international and national law, which is fundamental for its dealings with states and other international organizations, not least the UN, and for immunities and other international privileges.
The phytohormone auxin plays a crucial role in the development of so-called syncytia induced by cyst nematodes upon feeding on plant roots. However, it is unknown whether nematode-derived auxin contributes to plant parasitism by cyst nematodes. To do so, plant-parasitic nematodes should be able to produce and release auxin into the environment. Here, we investigated whether this is the case. Mass-spectrometry analyses show that the cyst nematode Globodera pallida is able to synthesize and release the auxin indole-3-acetic acid (IAA) and indicates that its biosynthesis can be stimulated by root diffusate. Using a collection of known auxin biosynthesis genes from well-studied pathways in bacteria and plants we revealed that in the genome of G. pallida candidate genes are present for 5 major biosynthesis pathways, which could be responsible for auxin production. RNA-seq data supported the genomic analysis and revealed the upregulation of various candidate biosynthesis genes during parasitic life stages of the nematode, suggesting a possible role in plant parasitism. However, genomic analysis within the phylum Nematoda showed that the potential auxin biosynthesis genes are wide-spread and also occur in bacterivorous, fungivorous, entomopathogenic and animal-parasitic nematodes. Therefore, our data show that G. pallida is able to synthesize and release auxin into the environment, but that potential auxin biosynthesis pathways are not unique for plant-parasitic nematodes. So, auxin biosynthesis may play a broader role in the life history of nematodes. However, a more specialized role for nematode-produced auxin in plant parasitism cannot be excluded and needs further investigation.
The archaeology of glaciers and ice patches has developed as a distinct new field in response to climate change and the melting of mountain ice. Thousands of artefacts and biological materials, dating back up to 10 000 years are being released from melting ice patches and retreating glaciers, offering unique insight into past human activities in cold environments. This paper examines the historical development of glacial archaeology, the preservation or loss of archaeological material from snow and ice, and the methodological challenges in locating and recovering such finds. Key finds and sites from North America, the Alps and Norway are presented. The emerging history demonstrates that high mountain areas were used more intensively in the past than previously assumed, including during winter. The paper argues that closer collaboration between glacial archaeology, glaciology and palaeoclimate research would be highly beneficial, particularly through joint investigations of the ice at glacial archaeological sites.
This article examines the relationship of the Argentine Socialist Party (PS) with international socialist organizations between 1889 and 1940. During this period, the PS emerged as the leading Latin American social-democratic organization and one of the few non-European members of both the Second International and the Labour and Socialist International. The article argues that the PS’s unique trajectory is best understood through the concept of “peripheral inter-nationalism”. This framework analyses how a socialist party in a non-colonial state built by mass European immigration engaged in a competitive nation-building project. The PS sought to construct its own version of the nation for a largely immigrant working class while simultaneously confronting the official nationalism being forged by the Argentine state. By analysing this dual challenge, the article complicates existing understandings of socialist “inter-nationalism”, revealing a distinct path to reconciling national and international loyalties. Drawing on archival research on the PS and the Internationals, the article shows how Argentine socialists actively translated and contested European norms, ultimately contributing to the historiography of international socialism by addressing the underexplored role of non-European parties.
Deep ice cores from polar ice sheets enable reconstructions of Earth’s past climate. Ice core records are therefore crucial for projecting future climate change, but our ability to interpret them relies on our understanding of polycrystalline-ice microstructures and mechanics. In turn, these microstructures enable modeling of ice flow and large-scale effects of ice sheet evolution. Since drilling began in the 1950s, the ice textures and climate proxies developed to decipher ice core records have been analyzed in one-dimensional (1D) or two-dimensional (2D) spaces, necessitated by the analytical instruments of core-processing lines and laboratories. Here, we develop a three-dimensional (3D), non-destructive approach to textural analysis that preserves the natural context of ice and complements standard methods. Our method combines lab-based absorption and diffraction contrast tomography to simultaneously visualize, measure, and spatially correlate ice grains and air bubbles from volumetric and 3D crystallographic perspectives, both lost during traditional sample preparations. We evaluate the representation of 3D versus 2D data and discuss how access to both c- and a-axis directions of grains may help constrain micromechanical models. We also built a specially designed cooling device for the laboratory X-ray system to extend observational volumes by several orders of magnitude over previous synchrotron-based measurements.
Can Ukraine avoid a frozen conflict with Russia, and could it have done so with more Western aid and victory in the war? Drawing on the Klosek et al. (2021) dataset of frozen conflicts, the paper outlines five criteria that are necessary to bring a frozen conflict to a military end. Two counterfactual scenarios explore whether increased or accelerated Western aid could have enabled Ukraine to meet these criteria. The analysis concludes that even with substantial Western assistance, Ukraine was unlikely to achieve the kind of victory needed to compel Russia to accept defeat and address the core issues. Ukraine’s victory-oriented approach was implausible not due to a lack of Western weapons, but because it failed to resolve entrenched political issues and lacked structural military advantages. The findings suggest that policy should emphasize diplomacy, while scholarship should explore why this unfeasible approach received strong backing.
We present results from the first application of the Global Navigation Satellite System (GNSS; e.g., the Global Positioning System, GPS) for radio beam calibration using a commercial GNSS receiver with the Deep Dish Development Array (D3A) at the Dominion Radio Astrophysical Observatory (DRAO). Several GNSS satellites pass through the main and sidelobes of the beam each day, enabling efficient mapping of the 2D beam structure. Due to the high SNR and abundance of GNSS satellites, we find evidence that GNSS can probe several sidelobes of the beam through repeatable measurements of the beam over several days. Over three days of measurements, the smallest observed difference in the primary beam’s main lobe was 0.56 dB-Hz. We also compare our results in the sidelobes to simulations and find rough agreement in shape. When scaling the observations and simulations to match the main lobe power levels, we find deviations in at least one of the first few nulls of approximately 5 dB or less. There is saturation in the main lobe for most satellites, which can likely be mitigated by better attenuation before the receiver input. We compare our work to other satellite systems that have been successful and are likely complementary to this technique. However, GNSS offers key advantages, including continuous transmission, broader frequency coverage relevant to CHORD, SKA-mid, and the DSA-2000, as well as more frequent satellite passes, making it a promising calibration method. These results also motivate further development of this technique for radio astronomy applications.
For Markov chains and Markov processes exhibiting a form of stochastic monotonicity (higher states have higher transition probabilities in terms of stochastic dominance), stability and ergodicity results can be obtained with the use of order-theoretic mixing conditions. We complement these results by providing quantitative bounds on deviations between distributions. We also show that well-known total variation bounds can be recovered as a special case.
In a semi-presidential system, which is the most common regime type in Europe, a separately elected president shares executive powers with the government. This dual-executive model incentivizes conflicts that reduce the capacity for effective decision-making. Alongside constitutional rules, the intraexecutive power balance is conditioned by informal practices in response to public opinion. Increasing public demand for a more powerful presidential role can thus ‘presidentialize’ dual executives. Utilizing novel survey data from Finland, we examine the factors that condition support for a stronger presidency. Relative to the country’s highly institutionalized and strongly government-driven political system, we find substantial support for a formally stronger and more confrontational presidency. This support is systematically connected with the typical features of a populist electorate (such as, for example, distrust in political institutions, male voters and ‘populist’ concerns) and we demonstrate that such respondents are also more willing to reduce the powers of parliamentary institutions. The strengthening of such attitudes can potentially destabilize semi-presidential regimes.
Learning a second language (L2) is challenging partly due to perceptual strategies inherited from learners’ first language. For example, speakers of tone languages like Mandarin over-use pitch in English prosody perception and production. We developed a novel training paradigm to help Mandarin learners adopt more native-like strategies by enhancing their use of duration relative to pitch cues during prosody categorization. After prosody training, participants used duration more during phrase boundary categorization but showed no clear change for contrastive focus and lexical stress, suggesting that cue weighting training is most effective when targeting a feature’s primary cue. The control group, who practiced English vocabulary, relied more on pitch in lexical stress categorization and phrase boundary production after training, suggesting that without targeted instruction, listeners default to existing strategies. Our findings demonstrate that although default strategies in L2 speech perception are difficult to resist, lifelong perceptual habits can be adjusted with training.
Within 18 months of its second consecutive general election (March 2018) as Italy's largest party, the valence populist 5-Star Movement (M5S) had dropped to polling 4th, halving its 30% + vote-share, behind parties of both the right and the left. In those 18-months, the party participated in two governments: one of the right and one of the centre-left. Two broad explanations for such decline are presented here: party credibility loss related to its (non)-ideological placement and penalties associated with incumbency. The former is predicted to lead those who initially supported the party to disengage from party preferences while the later is predicted to have respondents desert their preference for M5S to other parties. Using Italian panel survey data on partisan representation from March 2018 through September 2020, this manuscript identifies the opinions of those who those who deserted the party, those who disengaged from party preferences, and those who remained loyal to M5S. Descriptive analysis will first call attention to the differences between loyalists, deserters, the disengaged, and survey respondents more broadly. Multivariate analysis suggests the role of incumbency-based factors as an explanation for a decline in party support. The ideological position of the party (or being beyond left-and-right) had only a minor role. A discussion then focuses on the results of populists in power and the role of ideology in valence populism. Without an ideological core, once in power, voters punish (valence) populist party as they would any other, holding them to account for leadership and government performance.
This essay is part of an ongoing dialogue on INTERPOL’s role in international law and global governance. It argues that INTERPOL’s 2025 General Agreement on the Privileges and Immunities of the ICPO-INTERPOL (General Agreement)1 reflects a remarkable development in the multilateral recognition of international organizations.