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The growing utility and availability of genome-scale sequencing has led to increasingly broad incorporation across specialty disciplines of clinical research. However, classification of clinical relevance of genetic variation is an inherently clinical task, and the expertise to perform the necessary analysis, confirmation and reporting of these variants is not available in all research teams; consequently, disclosure of genomic variants to research participants remains challenging for many researchers. Advancing genomic medicine as a standard of care first requires institutional commitment and partnerships in supporting genomics in varied research studies that are inclusive of return of results to participants.
Materials and methods:
The University of North Carolina at Chapel Hill has vast experience with genetics in both clinical and research realms. By utilizing historical experience and input from key players, the Clinical GENomic analYSIS (GENYSIS) core facility was created as a case study and aims to provide a roadmap for research organizations to implement their own genomic sequencing core facilities.
Results:
The core has established a molecular sign-out conference, partnered with other core facilities on campus, and provides five main services: bioinformatics, variant analysis, clinical reporting, post-test services, and consultation with project advising. This paper presents case examples with discussion of continuous methodology improvements and embedded educational activities.
Conclusion:
This novel shared research resource enables clinical researchers with limited staff and genomics expertise to provide clinically relevant results to their study participants, expanding the reach of genomics research.
Australia and Canada have parallel submission processes allowing companies to submit dossiers to the respective health technology assessment (HTA) body before marketing authorization is issued, aiming to provide more timely access to drugs. This study investigated the associations of submission strategies with new active substance (NAS) rollout times and HTA recommendations.
Methods
This retrospective observational study analyzed HTA appraisals by the Pharmaceutical Benefits Advisory Committee (PBAC) and Canada’s Drug Agency (CDA-AMC) for NASs that received their first HTA recommendation between 2019 and 2023. Regulatory and HTA dates were sourced from public records. We implemented logistic regression to examine associations of HTA recommendation (optimal vs non-optimal). Linear regression was used to test associations of rollout time. Models were adjusted for submission sequence, country, therapeutic area, expedited review, conditional review, top R&D spenders, and year of HTA recommendation.
Results
229 HTA appraisals (126/229 parallel) were included. Parallel submissions were associated with a 14.0-month shorter rollout time compared to sequential submissions (p < 0.001). Rollout times in Canada were 6.0 months longer than those in Australia. Parallel submissions were associated with higher odds of receiving an optimal recommendation compared to sequential submissions (OR: 2.2; 95 percent CI: 1.2–4.2; p = 0.013). The odds of obtaining an optimal first HTA recommendation were higher in Canada than in Australia.
Conclusions
NASs following parallel submission showed faster rollout times than those following traditional sequential submission. Moreover, parallel submissions were associated with higher odds of receiving an optimal recommendation. These findings highlight the value of aligning regulatory and HTA processes.
The coupling between Rayleigh–Taylor (R–T) and Saffman–Taylor (S–T) instabilities, when a gas displaces a high-viscosity liquid, remains challenging to elucidate due to the unclear roles of density and viscosity contrasts. Counterintuitively, our radial Hele-Shaw cell experiments revealed that viscosity contrast – typically considered a damping factor – serves as the primary driver of instability. We observed that the glycerin–air interface, despite its higher viscosity, exhibits significantly greater instability than the water–air interface. This anomalous behaviour arises from the S–T mechanism, which accelerates the onset of nonlinearity and induces an early transition to fingering. We applied a unified model to decouple the competing influences of surface tension oscillation and viscous damping on R–T instability and the S–T destabilisation. Moreover, we proposed criteria for either mostly enhancing or completely freezing the instability. These findings offer valuable insights into manipulating hydrodynamic instabilities in contracting/expanding geometries through surface tension and viscosity.
High-intensity focused ultrasound (HIFU) is a non-invasive alternative to traditional surgery for detection and treatment. When HIFU targets a specific area, ultrasonic cavitation occurs with mechanical stress, causing tissue damage, a process that is significantly influenced by the surroundings. This paper presents a numerical study on the cavitation initiation and evolution mechanisms under focused ultrasonic waves considering the influence of a solid surface. Firstly, the dynamic property of focused ultrasonic waves and the generation of diffraction waves is explained based on the Huygens–Fresnel principle, and the prefocused phenomenon is analysed. Notably, the scenario considering the existence of a solid wall is discussed, with the corresponding cavitation clouds in a ‘tree-like’ pattern that can be generally divided into three or four subregions. The different initiation mechanisms of the near-wall cavitation clouds under a different relative distance between the theoretical focal point and the solid wall are discussed in detail. Finally, by considering the effects of the incident waves, scattered waves and their reflected waves on the solid wall, a wave superposition model is established that can clearly explain the distribution characteristics of the near-wall cavitation clouds with different modes. The understanding of the ultrasonic cavitation mechanism may support precise control in future HIFU applications.
This study revisits the long-standing consensus that the number and nature of basic-level administrative units in imperial China remained static over two millennia. It argues that this view underestimates the size and sophistication of field administration during the Northern Song dynasty (960–1127). During this period, towns (zhen) emerged as administrative centers, undertaking roles akin to the predominantly rural counties but within urban settings. Through a systematic analysis of the administrative functions of towns, this article reveals that approximately 30 percent of the 1,891 towns documented in 1085 were staffed by imperial officials and played a crucial role in delivering urban public goods such as fire prevention and law enforcement. In doing so, they supported the Song state’s extraordinary reliance on commercial taxation. These findings prompt a reassessment of the prevailing view in Chinese urban history that a disconnect between administration and commerce began during the Tang-Song transition.
Institutional investors conduct more governance research and are less likely to follow proxy advisor vote recommendations when a company’s bonds comprise a larger share of their assets. These findings are driven by bond holdings, shareholder proposals, and companies where fixed-income managers are more likely to be attentive and share an interest with equity investors in improving governance. The findings do not concentrate on companies or shareholder proposals where creditor–shareholder conflicts are likely. Overall, the findings suggest that corporate bond holdings influence how actively institutions monitor their equity positions and contribute to institutions’ overall incentive to be engaged stewards.
Regional survey of the Mountain Pine Ridge Forest Reserve, Cayo, Belize by the Rio Frio Regional Archaeological Project has revealed an expansive, ancient Maya granitic-rock extraction and ground stone tool crafting industry distributed across an 11 km2 region. To date, 16 extraction-workshop sites of varying size and compositional complexity totaling 100 ha or 1 km2 have been identified through a combination of ground-based reconnaissance and aerial LiDAR survey. This article introduces the two largest recorded to date, Buffalo Hill Quarries and Moshy’s Hill. Discussing them, we present an overview of the common attributes of the Mountain Pine Ridge quarry workshops including types of extraction sites (quarry pits, strip mines, and cut faces), structural components (bedrock pits and erected blocks), cached tools (hammerstones and pics), and discarded products (half-loaf and full-loaf forms and metates) found at them. As the type of sites presented here are new to archaeology, the article concludes with a series of questions to guide future work.
This article advances a story-driven, theoretical exploration of how entanglements of agony, exile and Land relations can reconfigure understandings of justice. Opening with autobiographical vignettes of “in-betweenness”, the article illuminates the unfolding of exilic life between Palestine and North America, naming the ruptures of writing about Palestine from afar as an ethical site of dwelling in the middle. Drawing on relational ontology, Indigenous and decolonial scholars, alongside posthumanist and new materialist thinkers, the article highlights convergences and dissonances in conceptualising Land as more than property: as kin, teacher and agentive being. From such relationality, this article argues that Land-bodied rights offer a framework for rethinking justice and education beyond the abstract, hierarchical assumptions of universal human rights, grounding learning in human and more-than-human relations. The final section explores diffractive pedagogies, suggesting that storytelling and more-than-human educational entanglements can foster an ethic of reciprocity and accountability towards the more-than-human justice. In envisioning rights through rupture, environmental education can become a site where ecological and decolonial justice are rethought and enacted through relational, Land-based and story-driven pedagogies.
While ethnographic observation has revealed nuances of ground stone production techniques and practical uses, there has been little theorizing about the archaeological exchange and movement of these goods or their deeper social meanings. In previous research, we obtained secure geochemical signatures for an ancient Maya ground stone tool assemblage by sourcing granite outcrops in Belize, enabling us to trace the provenience of certain archaeological assemblages. To understand the exchange mechanisms by which ground stone tools moved around the landscape, we explore three non-mutually exclusive models. We outline our expectations of material correlates for the archaeological record based on these exchange hypotheses and evaluate our assemblages against these expectations. This work helps broaden understandings of the organizational importance of ground stone tool production, exchange, and usage within ancient Maya society, critical first steps for investigating the socioeconomic dimensions of these tools.
This article outlines our research into granite use by the ancient Maya of the Alabama Townsite—a Late to Terminal Classic (ca. a.d. 700–900) rapid-growth community in East-Central Belize, part of the Eastern Maya Lowlands. One of our initial hypotheses regarding the seemingly sudden appearance of the town toward the end of the Late Classic period focused on granite as a staple resource exploited by its residents. We highlight current results of local geological surveys and related spatial, geochemical, and petrographic studies; preliminary analyses of surface-collected and excavated archaeological assemblages and architectural elements; and attempts at community-engaged experimental archaeology. We conclude that while ancient Alabamans did not extract granite as a staple resource for export, which could have fueled the community’s growth, they nonetheless valued granite in many ways, which we highlight in our discussion.
This paper presents the first experimental measurement of the Prandtl–Meyer function in the non-ideal compressible flow regime. Planar contoured nozzle profiles expand the flow to the supersonic regime, providing a uniform parallel flow of siloxane MM (hexamethyldisiloxane, $\textrm{C}_{6}\textrm{H}_{18}\textrm{OSi}_{2}$). Prandtl–Meyer expansions are then generated at sharp convex corners, for discrete flow deflection angles from 5$^\circ$ to 30$^\circ$. Stagnation pressures and temperatures are measured in the settling chamber, immediately upstream of the test section, to estimate the level of non-ideality of the investigated flows, ranging from mild non-ideal conditions to dilute ideal-gas states. Non-ideal thermodynamic effects through the expansions are characterised by means of independent measurements of Mach number by schlieren visualisations, and static pressure. Experimental comparisons across different thermodynamic states confirm the role of the compressibility factor evaluated at total conditions as a similarity parameter for moderately high non-ideal flows. To extract values of the Prandtl–Meyer function from the measurements, a simplified analytical model for the Prandtl–Meyer function dependency on the Mach number is formulated. The recovered values agree with Prandtl–Meyer theory, complemented with state-of-the-art thermodynamic models, for all the examined operating conditions.
Cluster environments influence galaxy evolution by curtailing star formation activity, notably through ram-pressure stripping (RPS). This process can leave observable signatures – such as gas tails and truncated gas discs – that are crucial for understanding how RPS affects galaxies. In this study, using spatially resolved spectroscopic data from the SAMI Galaxy Survey, we identify galaxies undergoing or recently affected by RPS in eight nearby clusters (${0.029\lt z\lt 0.058}$), through a visual classification scheme based on the ionised gas (H$\alpha$+[NII]$\lambda$6584) morphologies, split into ‘unperturbed’, ‘asymmetric’, and ‘truncated’. Alongside, we measure non-parametric structural parameters (concentration, asymmetry, and offset between gas and stars) to quantify the ionised gas morphologies. We find that combinations of parameters such as concentration, shape asymmetry, and stellar-ionised gas centre offsets are useful in categorising the degree of RPS in line with their ionised gas morphologies. The projected phase-space analysis shows that asymmetric galaxies are found in a narrow region in cluster-centric distance (${0.1\lt R/R_{200}\lt 0.6}$, where ${R}_{200}$ is the characteristic cluster radius) and have a larger dispersion in line-of-sight velocity ($\sigma(|v_{\text{pec}}|)_\mathrm{Asym} = 0.71^{+0.09}_{-0.07}\ \sigma_{200}$, with $\sigma_{200}$ being the cluster velocity dispersion within ${R}_{200}$), compared to the truncated and unperturbed samples that are more broadly distributed and predominantly located at larger cluster-centric distances. This suggests that asymmetric galaxies are likely recent infallers – having crossed within 0.5 $R{_{200}}$ in the past $\sim$1 Gyr. In terms of star formation, RPS candidates (asymmetric and truncated) yield a much steeper resolved star-forming main sequence (rSFMS; $\Sigma_\mathrm{SFR} - \Sigma_\ast$) relation compared to the unperturbed counterparts, primarily emerging from having lower $\Sigma_\mathrm{SFR}$ values for the low mass density regime (i.e. $\mathrm{log} \ \Sigma_\ast \lesssim 8 \ \mathrm{M}_\odot \ \mathrm{kpc^{-2}}$), with the steepest gradient deriving from the truncated sample. Moreover, radial specific star formation rate profiles introduce different trends for unperturbed and RPS candidates. Star formation in RPS candidates is suppressed in the outskirts relative to unperturbed galaxies and is more prominent for the truncated sample compared to the asymmetric counterparts. In contrast, central (i.e. ${r/r_{\text{eff}}} \lt 0.5$) star formation activity in RPS candidates is comparable with that in their unperturbed and field counterparts, suggesting no elevated activity. Taken together, this suggests an evolutionary trend linked to the RPS stage, where unperturbed galaxies likely represent recently accreted systems (pre-RPS), while asymmetric and truncated galaxies may correspond to populations undergoing RPS and post-RPS phases, respectively, favouring outside-in quenching.
Following the Wong Kim Ark decision in 1898, ethnic Chinese, other Asians, and almost all individuals born on U.S. soil secured the right to jus soli birthright citizenship. They could not, however, secure recognition of their citizenship without documentation, the key that linked birth to birthright. At a time when birth registration was not common, ethnic Chinese were able to establish U.S. citizenship in two main ways: through an order by a U.S. District Court or certification by U.S. immigration authorities.1 However, this documentation did not settle questions of the holder’s identity, immigration or citizenship status. Immigration inspectors generally doubted testimony given in these cases and believed that it was used to obtain fraudulent documentation of lawful immigration or citizenship status.
Birthright citizenship, as a common law principle, was a cornerstone of the American Republic at its founding.1 Like many “universal” rights at the time, it was presumed to apply to white people, routinely denied to enslaved people, and deeply contested for free people of color. After the Civil War, amid the effort to rebuild a fractured Union and answer the decades-long Black freedom struggle, Congress sought to affirm and extend the principle of birthright citizenship in the U.S. Constitution. In 1868, Congress recognized the ratification of the Fourteenth Amendment, extending citizenship to anyone born on U.S. soil. The language of the Fourteenth Amendment was clear: “All persons born or naturalized in the United States, and subject to the jurisdiction thereof, are citizens of the United States and of the State wherein they reside.”2 This included—as the congressional record reveals—the children of immigrants regardless of race, nationality, or desirability of their parents.3
This 2025 supplemental issue of Disaster Medicine and Public Health Preparedness (DMPHP) honors Dr. C. Norman (Norm) Coleman who dedicated his life to applying his expert knowledge of radiation to develop elegant, science-based solutions to incredibly complex problems such as the public health and medical response to radiological disasters and creating a corps of experts to provide quality cancer care for people in developing countries.
Understanding the possibility of future ice shelf collapses similar to that of the Larsen B is critical for improving sea-level-rise projections due to the restraint on upstream flow that ice shelves provide. Prior research has provided a criterion for assessing the vulnerability of ice shelves to hydrofracture. We apply these calculations to the model ensemble results from the Ice Sheet Modeling Intercomparison Project for CMIP6 (ISMIP6). With these ensemble results, we evaluate the predicted shelf vulnerability through time with forcings from several climate scenarios, climate models and basal melt parametrizations and with a range of fracture toughness values. Additionally, for the ISMIP6 experiments that included a collapse forcing (based on surface melt availability alone), we evaluate whether the ice subjected to the collapse forcing was vulnerable. We find that shelf vulnerability generally decreases through 2100 as ice thickness decreases, consistent with the predicted reduction in driving stress. Differences in initial vulnerability between models as well as sensitivity to fracture toughness, however, tend to outweigh the change from stress evolution. For the shelves where collapse was imposed in the corresponding ISMIP6 experiment (Larsen C, George VI, Wilkins), between 20$\%$ and 70$\%$ of collapsed shelf area was vulnerable depending on fracture toughness.