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We rework some of the die-swell singularity analysis for Stokes flow, originally by Ramalingam (Ramalingam, 1994 Fiber spinning and rheology of liquid-crystalline polymers, PhD thesis, Massachusetts Institute of Technology) in appendix A of his PhD thesis, in an attempt to demonstrate that for capillary numbers in the range $(0,\infty )$ the curvature may enter into the normal stress balance on the free surface and lead to separation angles exceeding $180^{\circ }$ and infinite curvature at the separation point. The singular coefficients in the asymptotic solution and the free surface shape in a neighbourhood of the separation point cannot be determined by a local analysis of the Michael type (Michael, Mathematika, vol. 5, 1958, pp. 82–84) but must be found from matching with the solution valid away from the die edge. The numerical method that we use in the truncated die-swell domain is a boundary element method incorporating the singular solution near the separation point. Although there is some variation in the extrudate swell ratios at different capillary numbers reported in the numerical literature, our results for capillary numbers $Ca$ from $1$ to $1000$ are within the range of values published in earlier papers. The computed separation angles at different values of $Ca$ agree well with the range of separation angles to be found in experimental and numerical papers. The separation angle appears to converge to a value different from $180^{\circ }$ as $Ca$ increases, leading us to conclude that the case of zero surface tension ($Ca=\infty$, with corresponding separation angle of $180^{\circ }$), is a singular limit.
OBJECTIVES/GOALS: Our goal is to explore and collaboratively identify the team science competencies essential for Clinical Research Professionals at all experience levels and how these competencies relate to the Joint Task Force for Clinical Translational Research Professionals Competencies. METHODS/STUDY POPULATION: Team science competencies for clinical research professionals are poorly defined. The JTF Clinical Trial Competencies lack sufficient emphasis on team science, though it is briefly included in two JTF competency domains: Leadership & Professionalism, and Communication & Teamwork. The competencies primarily focus on tasks related to clinical research and basic knowledge of product development; however, a conceptual model for applying the competencies using a team science lens is needed. Currently, the JTF competency figure is often thought of as sequential, given the competencies are numbered, creating the misconception that the last competencies are less important. We support a new figure showing the permeability of team science across competencies and the connectedness and equality of the competencies. RESULTS/ANTICIPATED RESULTS: Our anticipated results are to show the integral nature of team science in clinical research professional communities of practice. Once complete, we will have identified measurable team science competency-based skills essential for clinical research professionals at various levels of expertise. Understanding the multi-dimensional team science competencies will inform targeted team science education and training for clinical research professionals. Our revised competency framework provides an improved team science conceptual model for clinical translational science. DISCUSSION/SIGNIFICANCE: Our work will define team science competencies as related to clinical research professionals at all experience levels. The interdependence of teams across clinical trial activities necessitates a consideration of an improved conceptual framework for clinical translational team science competencies.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Background: Antibiotics are not recommended but are often prescribed for upper respiratory-tract infections (URIs). Prescribers cite patient expectation as a driver of inappropriate antibiotic prescribing; prior literature has demonstrated higher satisfaction scores in patients who receive antibiotics compared to those who do not. We assessed whether veteran satisfaction at URI visits was associated with antibiotic receipt or with reported expectation for antibiotics. Methods: We surveyed veterans with documented URI encounters in the Veterans’ Affairs Tennessee Valley Healthcare System between January 1, 2018, and December 31, 2019. Patients not evaluated in person, with documented dementia, or who died prior to the study start date were excluded. Veterans were asked to recall their URI visit and to complete the Patient Safety Questionnaire (PSQ)-18 (Rand Corporation) and questions assessing antibiotic expectations. The PSQ-18, an 18-item survey that assesses patient satisfaction, uses a 5-point Likert scale (ie, strongly disagree, disagree, uncertain, agree, strongly agree), yielding a composite score of 18–90. Higher scores represent more satisfaction with care. Demographic and visit-specific information were extracted via chart review. We used multivariable linear regression to assess differences in composite PSQ-18 satisfaction scores between those who did and did not receive an antibiotic, adjusted for patient and visit characteristics, and to assess differences in satisfaction scores for those who did and did not report expecting antibiotics, adjusted for antibiotic receipt. Results: We identified 1,435 patients seen for URI at 17 sites. After exclusions, 1,343 veterans were eligible for chart abstraction. After excluding 42 responders who responded after study close or returned blank surveys, the final analytic cohort included 432 (32.2%) of 1,343 responders; 225 (52.1%) received an antibiotic and 207 (47.9%) did not. Mean total satisfaction for veterans who received an antibiotic was 67.8 (SD, ±9.4) compared to 66.7 (SD, ±9.7) for those who did not (Figure 1). Increased total satisfaction was not significantly associated with antibiotic receipt (0.65; 95% CI, −2.0 to 3.3). Most veterans (72.0%) disagreed that visit satisfaction depended on antibiotic receipt. However, only 30.8% reported that they would not expect an antibiotic for URI visits. A significant reduction in total satisfaction (−4.1; 95% CI, −6.3 to −1.9) was associated with expecting compared to not expecting an antibiotic. Conclusions: Our findings suggest that prescribing an antibiotic is not associated with increased veteran satisfaction for URI visits but is associated with expecting an antibiotic. Future work will evaluate methods to change veteran antibiotic expectations.
In March 2020, at the onset of the coronavirus disease 2019 (COVID-19) pandemic in the United States, the Southern California Extracorporeal Membrane Oxygenation (ECMO) Consortium was formed. The consortium included physicians and coordinators from the 4 ECMO centers in San Diego County. Guidelines were created to ensure that ECMO was delivered equitably and in a resource effective manner across the county during the pandemic. A biomedical ethicist reviewed the guidelines to ensure ECMO use would provide maximal community benefit of this limited resource. The San Diego County Health and Human Services Agency further incorporated the guidelines into its plans for the allocation of scarce resources. The consortium held weekly video conferences to review countywide ECMO capacity (including census and staffing), share data, and discuss clinical practices and difficult cases. Equipment exchanges between ECMO centers maximized regional capacity. From March 1 to November 30, 2020, consortium participants placed 97 patients on ECMO. No eligible patients were denied ECMO due to lack of resources or capacity. The Southern California ECMO Consortium may serve as a model for other communities seeking to optimize ECMO resources during the current COVID-19 or future pandemics.
We use three-dimensional (3-D) fully kinetic particle-in-cell simulations to study the occurrence of magnetic reconnection in a simulation of decaying turbulence created by anisotropic counter-propagating low-frequency Alfvén waves consistent with critical-balance theory. We observe the formation of small-scale current-density structures such as current filaments and current sheets as well as the formation of magnetic flux ropes as part of the turbulent cascade. The large magnetic structures present in the simulation domain retain the initial anisotropy while the small-scale structures produced by the turbulent cascade are less anisotropic. To quantify the occurrence of reconnection in our simulation domain, we develop a new set of indicators based on intensity thresholds to identify reconnection events in which both ions and electrons are heated and accelerated in 3-D particle-in-cell simulations. According to the application of these indicators, we identify the occurrence of reconnection events in the simulation domain and analyse one of these events in detail. The event is related to the reconnection of two flux ropes, and the associated ion and electron exhausts exhibit a complex 3-D structure. We study the profiles of plasma and magnetic-field fluctuations recorded along artificial-spacecraft trajectories passing near and through the reconnection region. Our results suggest the presence of particle heating and acceleration related to small-scale reconnection events within magnetic flux ropes produced by the anisotropic Alfvénic turbulent cascade in the solar wind. These events are related to current structures of the order of a few ion inertial lengths in size.
It is very difficult to know how international social linkages affect domestic ideological polarization because we can never observe polarization occurring both with and without international connections. To estimate this missing counterfactual, we employ a new statistical method based on Bayesian item-response theory that permits us to disaggregate polarization after the Arab Uprisings into domestic and transnational components. We collected a dataset of Twitter accounts in Egypt and Tunisia during the critical year of 2013, when the Egyptian military overthrew the Islamist President Mohamed Morsi. We find that the coup increased retweets among Egyptian ideological allies by 50% each day following the coup and decreased cross-ideological retweets by 25%. Tunisian Twitter communities also showed stronger intragroup retweeting although at lower levels than in Egypt. Counter-intuitively, our model shows that the additional polarization in Tunisia after the coup appears to have dampened further polarization among Islamists in Egypt.
This study aimed to examine the predictors of cognitive performance in patients with pediatric mild traumatic brain injury (pmTBI) and to determine whether group differences in cognitive performance on a computerized test battery could be observed between pmTBI patients and healthy controls (HC) in the sub-acute (SA) and the early chronic (EC) phases of injury.
Method:
203 pmTBI patients recruited from emergency settings and 159 age- and sex-matched HC aged 8–18 rated their ongoing post-concussive symptoms (PCS) on the Post-Concussion Symptom Inventory and completed the Cogstate brief battery in the SA (1–11 days) phase of injury. A subset (156 pmTBI patients; 144 HC) completed testing in the EC (~4 months) phase.
Results:
Within the SA phase, a group difference was only observed for the visual learning task (One-Card Learning), with pmTBI patients being less accurate relative to HC. Follow-up analyses indicated higher ongoing PCS and higher 5P clinical risk scores were significant predictors of lower One-Card Learning accuracy within SA phase, while premorbid variables (estimates of intellectual functioning, parental education, and presence of learning disabilities or attention-deficit/hyperactivity disorder) were not.
Conclusions:
The absence of group differences at EC phase is supportive of cognitive recovery by 4 months post-injury. While the severity of ongoing PCS and the 5P score were better overall predictors of cognitive performance on the Cogstate at SA relative to premorbid variables, the full regression model explained only 4.1% of the variance, highlighting the need for future work on predictors of cognitive outcomes.
Electrochemical treatments, such as electropolishing on titanium alloys, are used to promote the formation of nanostructured surfaces, which can contribute to the bone regeneration process. However, sterilization methods can change the superficial and physicochemical properties of the biomaterials. The objective of this work was to evaluate the effect of three sterilization methods (air plasma, ethanol + PBS, and autoclave sterilizations) on nanostructured Ti6Al4V surfaces properties obtained by electrochemical treatment. These methods, especially the first two, have been widely used in literature, yet few studies in the literature highlight the changes on the surface of the samples. The nanostructures were obtained by electropolishing in a H2SO4/HF/glycerine solution, at 25 V and at 7 °C for 4 min. Samples were characterized by atomic force microscopy (AFM), profilometry, and wettability. Samples were seeded with hESC-MPs, and the cell number was measured. The air plasma sterilization did not promote changes in nanometric morphology and roughness of the Ti6Al4V nanostructured samples. Unlike air plasma sterilization, the ethanol + PBS and the autoclave sterilizations, which strongly affected the nanostructured surface morphology and properties, and, consequently, the cellular viability after 7 days of contact with human embryonic stem cell-derived mesenchymal progenitors (hESC-MPs).
The crystal structure of tlapallite has been determined using single-crystal X-ray diffraction and supported by electron probe micro-analysis, powder diffraction and Raman spectroscopy. Tlapallite is trigonal, space group P321, with a = 9.1219(17) Å, c = 11.9320(9) Å and V = 859.8(3) Å3, and was refined to R1 = 0.0296 for 786 reflections with I > 2σ(I). This study resulted from the discovery of well-crystallised tlapallite at the Wildcat prospect, Utah, USA. The chemical formula of tlapallite has been revised to (Ca,Pb)3CaCu6[Te4+3Te6+O12]2(Te4+O3)2(SO4)2·3H2O, or more simply (Ca,Pb)3CaCu6Te4+8Te6+2O30(SO4)2·3H2O, from H6(Ca,Pb)2(Cu,Zn)3(TeO3)4(TeO6)(SO4). The tlapallite structure consists of layers containing distorted Cu2+O6 octahedra, Te6+O6 octahedra and Te4+O4 disphenoids (which together form the new mixed-valence phyllotellurate anion [Te4+3Te6+O12]12−), Te4+O3 trigonal pyramids and CaO8 polyhedra. SO4 tetrahedra, Ca(H2O)3O6 polyhedra and H2O groups fill the space between the layers. Tlapallite is only the second naturally occurring compound containing tellurium in both the 4+ and 6+ oxidation states with a known crystal structure, the other being carlfriesite, CaTe4+2Te6+O8. Carlfriesite is the predominant secondary tellurium mineral at the Wildcat prospect. We also present an updated structure for carlfriesite, which has been refined to R1 = 0.0230 for 874 reflections with I > 2σ(I). This updated structural refinement improves upon the one reported previously by refining all atoms anisotropically and presenting models of bond valence and Te4+ secondary bonding.
One of the founding concepts of the high-entropy alloy (HEA) field was that the lattice structures of multicomponent solid solution phases are highly distorted. The displacement of the constituent atoms, away from their ideal locations (local lattice strain), has been widely cited as the reason for a number of the observed physical and mechanical properties. However, very little data directly characterizing these lattice distortions exist and, thus, the validity of this hypothesis remains an open question. Here, the concept is reviewed by considering the underlying principles of the lattice distortions, the suitability of different assessment methods, and the direct experimental data currently available. It is found that, at present, there is no clear evidence that the lattice distortions in HEAs are significantly greater than those of conventional alloys. However, so few alloys have been appropriately characterized that this conclusion cannot be considered overarching and further research is required.
Building on the recent advances in next-generation sequencing, the integration of genomics, proteomics, metabolomics, and other approaches hold tremendous promise for precision medicine. The approval and adoption of these rapidly advancing technologies and methods presents several regulatory science considerations that need to be addressed. To better understand and address these regulatory science issues, a Clinical and Translational Science Award Working Group convened the Regulatory Science to Advance Precision Medicine Forum. The Forum identified an initial set of regulatory science gaps. The final set of key findings and recommendations provided here address issues related to the lack of standardization of complex tests, preclinical issues, establishing clinical validity and utility, pharmacogenomics considerations, and knowledge gaps.
This article explores the settling and unsettling of legal concepts in relation to refugee-status determination. To gain admission to the United States, asylum seekers are required to demonstrate a well-founded fear of persecution on the basis of one of five protected grounds: race, religion, nationality, political opinion, or membership in a particular social group. Accordingly, many political asylum claims turn on the interpretation of “particular social group.” This article examines case law disputes in the federal courts of appeals over the meaning of that phrase and describes how statutory interpretation by judges has contributed to the persistence of such disputes over several decades since the passage of the 1980 Refugee Act. My analysis reveals the tensions between different forms of rationality at play in judicial statutory interpretation and applies the concept of legal settling to a new empirical domain.
Ti6Al4V alloys usually need to undergo some kind of surface treatment to enable good bone growth and implant integration. In this work, three treatments that modify the titanium alloy surface were studied with the aim of promoting osteogenic differentiation of human-embryonic-stem-cell-derived mesenchymal progenitors (hESC-MPs). The surface treatments used were mechanical polishing and electropolishing for 4 or 12 min in an H2SO4/HF/glycerine solution. The samples were characterised by atomic force microscopy, profilometry, X-ray photoelectron spectroscopy, and wettability. Samples were seeded with hESC-MPs in osteogenic media, and the cell number and alkaline phosphatase activity were measured. The electropolishing surface treatments influenced the nanometric morphology and wettability. However, the electropolished surfaces contributed in the same way as the mechanically polished surface to osteogenic differentiation, indicating that differentiation was strongly influenced by microroughness, which did not differ among the treatments used in the present work.
To examine two hypotheses about the longitudinal relationship between night-time parenting behaviours in the first few postnatal weeks and infant night-time sleep-waking at five weeks, three months and six months of age in normal London home environments.
Background
Most western infants develop long night-time sleep periods by four months of age. However, around 20–30% of infants in many countries continue to sleep for short periods and cry out on waking in the night: the most common type of infant sleep behaviour problem. Preventive interventions may help families and improve services. There is evidence that ‘limit-setting’ parenting, which is common in western cultures, supports the development of settled infant night-time behaviour. However, this evidence has been challenged. The present study measures three components of limit-setting parenting (response delay, feeding interval, settling method), examines their stability, and assesses the predictive relationship between each of them and infant sleep-waking behaviours.
Methods
Longitudinal observations comparing a General-Community (n=101) group and subgroups with a Bed-Sharing (n=19) group on infra-red video, diary and questionnaire measures of parenting behaviours and infant feeding and sleep-waking at night.
Findings
Bed-Sharing parenting was highly infant-cued and stable. General-Community parenting involved more limit-setting, but was less stable, than Bed-Sharing parenting. One element of General-Community parenting – consistently introducing a short interval before feeding – was associated with the development of longer infant night-time feed intervals and longer day-time feeds at five weeks, compared with other General-Community and Bed-Sharing infants. Twice as many General-Community infants whose parents introduced these short intervals before feeding in the early weeks slept for long night-time periods at three months of age on both video and parent-report measures, compared with other General-Community and Bed-Sharing infants. The findings’ implications for our understanding of infant sleep-waking development, parenting programmes, and for practice and research, are discussed.
To provide descriptive figures for infant distress and associated parenting at night in normal London home environments during the first three months of age.
Background
Most western infants develop long night-time sleep periods by four months of age. However, 30% of infants in many countries sleep for short periods and cry out on waking in the night: the most common type of infant sleep behaviour problem. Preventive interventions may help families and improve services. There is evidence that ‘limit-setting’ parenting, which is common in western cultures, supports the development of settled infant night-time behaviour. However, a recent review has challenged this and argued that this form of parenting risks distressing infants. This study describes limit-setting parenting as practiced in London, compares it with ‘infant-cued’ parenting and measures the associated infant distress.
Methods
Longitudinal infrared video, diary and questionnaire observations comparing a General-Community (n=101) group and subgroups with a Bed-Sharing (n=19) group on measures of infant and parenting behaviours at night.
Findings
General-Community parents took longer to detect and respond to infant waking and signalling, and to begin feeding, compared with the highly infant-cued care provided by Bed-Sharing parents. The average latency in General-Community parents’ responding to infant night-time waking was 3.5 min, during which infants fuss/cried for around 1 min. Compared with Bed-Sharing parenting, General-Community parenting was associated with increased infant distress of around 30 min/night at two weeks, reducing to 12 min/night by three months of age. However, differences in infant distress between General-Community subgroups adopting limit-setting versus infant-cued parenting were not large or statistically significant at any age. The figures provide descriptive evidence about limit-setting parenting which may counter some doubts about this form of parenting and help parents and professionals to make choices.
Edited by
Ian Convery, Professor of Conservation & Forestry, Centre for Wildlife Conservation, University of Cumbria.,Peter Davis, Emeritus Professor of Museology, University of Newcastle
Edited by
Ian Convery, Professor of Conservation & Forestry, Centre for Wildlife Conservation, University of Cumbria.,Peter Davis, Emeritus Professor of Museology, University of Newcastle
The concepts of nature, culture and heritage are deeply entwined; their threads run together in some of our finest museums, in accounts of exploration and discovery, in the work of artists, poets andwriters, and in areas that are cherished and protected because of their landscapes and wildlife. The conservation ethic - placing a value on the natural environment - lies at the heart of the notion of "natural heritage", but we need to question how those values originated, were consolidated and ultimately moulded and changed over time. In a contemporary context the connections between nature andculture have sometimes become lost, fragmented, dislocated or misunderstood; where did "natural heritage" begin and how do we engage with the idea of "nature" today? The essays collected here re-evaluate the role of culture in developing the concept of natural heritage, reflecting on the shifts in its interpretation over the last 300 years.
Contributors: Martin Holdgate, Marie Addyman,E. Charles Nelson, Darrell Smith, Andrew Ramsey, Viktor Kouloumpis, Richard Milner, Gina Douglas, Penny Bradshaw, Arthur MacGregor, Chiara Nepi, Hannah Paddon, Stephen Hewitt, Gordon McGregor Reid, Ghillean T Prance, Peter Davis, Christopher Donaldson, Lucy McRobert, Sophie Darlington, Keith Scholey, Paul A. Roncken, Angus Lunn, Juliet Clutton-Brock, Tim Sands, Robert A. Lambert, James Champion,Erwin van Maanen, Heather Prince, Chris Loynes, Julie Taylor, Sarah Elmeligi, Samantha Finn, Owen Nevin, Jared Bowers, Kate Hennessy, Natasha Lyons, Mike Jeffries.
Edited by
Ian Convery, Professor of Conservation & Forestry, Centre for Wildlife Conservation, University of Cumbria.,Peter Davis, Emeritus Professor of Museology, University of Newcastle