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Two-dimensional Euler flows, in the plane or on simple surfaces, possess a material invariant, namely the scalar vorticity normal to the surface. Consequently, flows with piecewise-uniform vorticity remain that way, and moreover evolve in a way which is entirely determined by the instantaneous shapes of the contours (interfaces) separating different regions of vorticity – this is known as ‘contour dynamics’. Unsteady vorticity contours or interfaces often grow in complexity (lengthen and fold), either as a result of vortex interactions (like mergers) or ‘filamentation’. In the latter, wave disturbances riding on a background, equilibrium contour shape appear to inevitably steepen and break, forming filaments, repeatedly– and perhaps endlessly. Here, we revisit the onset of filamentation. Building upon previous work and using a weakly nonlinear expansion to third order in wave amplitude, we derive a universal, parameter-free amplitude equation which applies (with a minor change) both to a straight interface and a circular patch in the plane, as well as circular vortex patches on the surface of a sphere. We show that this equation possesses a local, self-similar form describing the finite-time blow up of the wave slope (in a re-scaled long time proportional to the inverse square of the initial wave amplitude). We present numerical evidence for this self-similar blow-up solution, and for the conjecture that almost all initial conditions lead to finite-time blow up. In the full contour dynamics equations, this corresponds to the onset of filamentation.
We report a case of hypoplastic left heart syndrome and with subsequent aortopathy and then found to have hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome due to a germline SMAD4 pathologic variant. The patient’s staged palliation was complicated by the development of neoaortic aneurysms, arteriovenous malformations, and gastrointestinal bleeding thought to be secondary to Fontan circulation, but workup revealed a SMAD4 variant consistent with hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome. This case underscores the importance of genetic modifiers in CHD, especially those with Fontan physiology.
Systems Engineering (SE) is becoming increasingly relevant in industrial application since more stakeholders are involved in engineering activities. To implement SE, companies have to adapt existing engineering processes and methods. This adaption requires knowledge about new methods as well as their integration into the engineering activities. In order to ensure goal-oriented identification of methods for different SE activities in this contribution an action field profile and the Systems Engineering Method Matrix are proposed. The development of both tools is driven by the assumption that most SE activities and methods can be described based on the artefacts the deliver. In order to get feedback about the proposed tools, semi-structured interviews with two industry partners were conducted, focussing on the tool's usability. These interviews underline the basic usability of the tools and their support to identify SE activities to be supported by (new) methods. Moreover, requirements for further development and adaption are derived from the interviews.
The scientific study of Neolithic monuments holds fundamental keys to the analysis of early social complexity. This is often impeded by the challenges involved in understanding their temporality and, particularly, their initial construction dates. This problem is most severe in monuments that were not predominantly used for burial and went on to have long biographies in which activity in later periods obliterated the material record of the earliest phases. That was certainly the case of the Menga dolmen, part of the Antequera World Heritage site (Málaga, Spain), and one of the most remarkable megaliths in Europe, for which, after nearly 200 years of explorations and research, no firm chronology existed. The research presented in this paper shows how this problem was tackled through a multimethod, scientific, and geoarchaeological approach. The analysis of 29 fresh numerical ages, including radiocarbon determinations as well as optically stimulated luminescence, thermoluminescence, and uranium-thorium dates, led to the successful establishment of Menga's construction date and the subsequent contextualization of the monument within the social and cultural background it arose in. Placing the dolmen in the context of its time of “birth” introduces entirely new possibilities for its interpretation, both in terms of local and supralocal social and cultural processes.
We report on the generation and delivery of 10.2 PW peak power laser pulses, using the High Power Laser System at the Extreme Laser Infrastructure – Nuclear Physics facility. In this work we demonstrate for the first time, to the best of our knowledge, the compression and propagation of full energy, full aperture, laser pulses that reach a power level of more than 10 PW.
In this manuscript, we discuss the implementation and deployment of mobile integrated health and community paramedicine (MIH/CP) testing sites to provide screening, testing, and community outreach during the first months of the 2019 coronavirus disease (COVID-19) pandemic in the metropolitan region of Charlotte, North Carolina. This program addresses the need for an agile testing strategy during the current pandemic. We disclose the number of patients evaluated as “persons under investigation” and the proportion with positive severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) results from these sites. We describe how the programs were applied to patient care and include considerations on how additional staffing, scalability, and flexibility of these services may be applied to future patient and health care crises.
Methods:
This is a descriptive report of the implementation of MIH/CP test sites in our health care system’s early response to the COVID-19 pandemic in March 2020. Retrospective data on the number of patients and their associated demographics are reported here as raw data. No statistical analysis was performed.
Results:
Between March 15, 2020, and April 15, 2020, our 6 MIH/CP test sites evaluated 4342 patients. Of these, 401 patients (9.2%) had positive test results, 62.8% of whom were women. The estimated duration of each patient encounter under investigation was 3 to 5 minutes. The paramedics were able to perform a brief history, specific physical examination, and screening for signs of hypoxemic respiratory failure. There were no cases of accidental exposure or failure of personal protective equipment for the MIH/CP paramedics.
Conclusions:
In our health care system, we pivoted the traditional MIH/CP model to rapidly initiate remote drive-through testing for COVID-19 in pre-screened individuals. This model allowed us to test patients with suspected COVID-19 patients away from traditional health care sites and mitigate exposure to health care workers and other patients.
In the 2015 review paper ‘Petawatt Class Lasers Worldwide’ a comprehensive overview of the current status of high-power facilities of ${>}200~\text{TW}$ was presented. This was largely based on facility specifications, with some description of their uses, for instance in fundamental ultra-high-intensity interactions, secondary source generation, and inertial confinement fusion (ICF). With the 2018 Nobel Prize in Physics being awarded to Professors Donna Strickland and Gerard Mourou for the development of the technique of chirped pulse amplification (CPA), which made these lasers possible, we celebrate by providing a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed. We are now in the era of multi-petawatt facilities coming online, with 100 PW lasers being proposed and even under construction. In addition to this there is a pull towards development of industrial and multi-disciplinary applications, which demands much higher repetition rates, delivering high-average powers with higher efficiencies and the use of alternative wavelengths: mid-IR facilities. So apart from a comprehensive update of the current global status, we want to look at what technologies are to be deployed to get to these new regimes, and some of the critical issues facing their development.
Introduction: Children diagnosed with medulloblastoma (MB) who are refractory to upfront therapy or experience recurrence have very poor prognoses. Although phase I and phase II trials exist, these treatments bear significant treatment-related morbidity and mortality. Methods: A retrospective review of children diagnosed with a recurrence of MB from 2002 to 2015 at McMaster University was undertaken. Results: Recurrent disease in 10 patients involved leptomeningeal dissemination, with 3 experiencing local recurrence. In three recurrent patients the disease significantly progressed, and the children were palliated. The remaining 10 children underwent some form of salvage therapy, including surgical re-resection, radiation, and chemotherapy, either in isolation or in varying combinations. Of the 13 children experiencing treatment-refractory or recurrent disease, 4 are currently alive with a median follow-up of 38.5 months (75.5 months). Of the eight patients with molecular subgrouping data, none of the Wnt MB experienced recurrence. Conclusion: Recurrent MB carried a poor prognosis with a 5-year overall survival (OS) of 18.2% despite the administration of salvage therapy. The upfront therapy received, available treatment, and tolerability of the proposed salvage therapy resulted in significant heterogeneity in the treatment of our recurrent cohort.
With the intention to inform future public health initiatives, we aimed to determine the extent to which typical childhood dietary trajectories predict adolescent cardiovascular phenotypes.
Design
Longitudinal study. Exposure was determined by a 4 d food diary repeated over eight waves (ages 4–15 years), coded by Australian Dietary Guidelines and summed into a continuous diet score (0–14). Outcomes were adolescent (Wave 8, age 15 years) blood pressure, resting heart rate, pulse wave velocity, carotid intima-media thickness, retinal arteriole-to-venule ratio. Latent class analysis identified ‘typical’ dietary trajectories from childhood to adolescence. Adjusted linear regression models assessed relationships between trajectories and cardiovascular outcomes, adjusted for a priori potential confounders.
Setting
Community sample, Melbourne, Australia.
Subjects
Children (n 188) followed from age 4 to 15 years.
Results
Four dietary trajectories were identified: unhealthy (8 %); moderately unhealthy (25 %); moderately healthy (46 %); healthy (21 %). There was little evidence that vascular phenotypes associated with the trajectories. However, resting heart rate (beats/min) increased (β; 95 % CI) across the healthy (reference), moderately healthy (4·1; −0·6, 8·9; P=0·08), moderately unhealthy (4·5; −0·7, 9·7; P=0·09) and unhealthy (10·5; 2·9, 18·0; P=0·01) trajectories.
Conclusions
Decade-long dietary trajectories did not appear to influence macro- or microvascular structure or stiffness by mid-adolescence, but were associated with resting heart rate, suggesting an early-life window for prevention. Larger studies are needed to confirm these findings, the threshold of diet quality associated with these physiological changes and whether functional changes in heart rate are followed by phenotypic change.
We consider finite $2$-complexes $X$ that arise as quotients of Fuchsian buildings by subgroups of the combinatorial automorphism group, which we assume act freely and cocompactly. We show that locally CAT($-1$) metrics on $X$, which are piecewise hyperbolic and satisfy a natural non-singularity condition at vertices, are marked length spectrum rigid within certain classes of negatively curved, piecewise Riemannian metrics on $X$. As a key step in our proof, we show that the marked length spectrum function for such metrics determines the volume of $X$.
We have previously shown that the minor alleles of vascular endothelial growth factor A (VEGFA) single-nucleotide polymorphism rs833069 and superoxide dismutase 2 (SOD2) single-nucleotide polymorphism rs2758331 are both associated with improved transplant-free survival after surgery for CHD in infants, but the underlying mechanisms are unknown. We hypothesised that one or both of these minor alleles are associated with better systemic ventricular function, resulting in improved survival.
Methods
This study is a follow-up analysis of 422 non-syndromic CHD patients who underwent neonatal cardiac surgery with cardiopulmonary bypass. Echocardiographic reports were reviewed. Systemic ventricular function was subjectively categorised as normal, or as mildly, moderately, or severely depressed. The change in function was calculated as the change from the preoperative study to the last available study. Stepwise linear regression, adjusting for covariates, was performed for the outcome of change in ventricular function. Model comparison was performed using Akaike’s information criterion. Only variables that improved the model prediction of change in systemic ventricular function were retained in the final model.
Results
Genetic and echocardiographic data were available for 335/422 subjects (79%). Of them, 33 (9.9%) developed worse systemic ventricular function during a mean follow-up period of 13.5 years. After covariate adjustment, the presence of the VEGFA minor allele was associated with preserved ventricular function (p=0.011).
Conclusions
These data support the hypothesis that the mechanism by which the VEGFA single-nucleotide polymorphism rs833069 minor allele improves survival may be the preservation of ventricular function. Further studies are needed to validate this genotype–phenotype association and to determine whether this mechanism is related to increased vascular endothelial growth factor production.
Ten ice-sheet models are used to study sensitivity of the Greenland and Antarctic ice sheets to prescribed changes of surface mass balance, sub-ice-shelf melting and basal sliding. Results exhibit a large range in projected contributions to sea-level change. In most cases, the ice volume above flotation lost is linearly dependent on the strength of the forcing. Combinations of forcings can be closely approximated by linearly summing the contributions from single forcing experiments, suggesting that nonlinear feedbacks are modest. Our models indicate that Greenland is more sensitive than Antarctica to likely atmospheric changes in temperature and precipitation, while Antarctica is more sensitive to increased ice-shelf basal melting. An experiment approximating the Intergovernmental Panel on Climate Change’s RCP8.5 scenario produces additional first-century contributions to sea level of 22.3 and 8.1 cm from Greenland and Antarctica, respectively, with a range among models of 62 and 14 cm, respectively. By 200 years, projections increase to 53.2 and 26.7 cm, respectively, with ranges of 79 and 43 cm. Linear interpolation of the sensitivity results closely approximates these projections, revealing the relative contributions of the individual forcings on the combined volume change and suggesting that total ice-sheet response to complicated forcings over 200 years can be linearized.
Thin films of organic semiconductor PEDOT:PSS deposited onto silicon and fusedsilica substrates. These films were then treated with sulfuric acid(H2SO4) for various amounts of time (i.e., 10, 20, 40,60, and 80 minutes). Preliminary results obtained with FT-IR, UV-VIS, and VanDerPauw conductivity methods suggest that the H2SO4removes the PSS isonomer from the PEDOT:PSS system. This PSS removal alsoinduces a decrease in film thickness.
The environmental impact resulting from the use of fossil fuel as an energy source affects the entire globe. Eventually, fossil fuels will no longer be a reasonable source of energy and alternative energy sources will be needed. Thermoelectric materials (TE) that directly convert heat into electricity are a viable option to replace the conventional fossil fuel because they are reliable, cost effective, and use no moving parts. Recently researchers discovered the existence of giant Seebeck coefficient in manganese oxide (MnO2) powders, which ignited an increased interest in MnO2-based materials. In this work we present a systematic structural and electrical characterization of amorphous and crystalline MnxOy thin films. These films were deposited at room temperature on heated silicon and sapphire substrates by DC Magnetron Sputtering. Our preliminary results show that MnxOy/silicon thin films undergo a crystalline change from Mn2O3 to Mn3O4 as annealing temperature is increased from 300°C to 500°C.
Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD).
Methods:
In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression.
Results:
Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure.
Conclusions:
We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.
Agitation is common across neuropsychiatric disorders and contributes to disability, institutionalization, and diminished quality of life for patients and their caregivers. There is no consensus definition of agitation and no widespread agreement on what elements should be included in the syndrome. The International Psychogeriatric Association formed an Agitation Definition Work Group (ADWG) to develop a provisional consensus definition of agitation in patients with cognitive disorders that can be applied in epidemiologic, non-interventional clinical, pharmacologic, non-pharmacologic interventional, and neurobiological studies. A consensus definition will facilitate communication and cross-study comparison and may have regulatory applications in drug development programs.
Methods:
The ADWG developed a transparent process using a combination of electronic, face-to-face, and survey-based strategies to develop a consensus based on agreement of a majority of participants. Nine-hundred twenty-eight respondents participated in the different phases of the process.
Results:
Agitation was defined broadly as: (1) occurring in patients with a cognitive impairment or dementia syndrome; (2) exhibiting behavior consistent with emotional distress; (3) manifesting excessive motor activity, verbal aggression, or physical aggression; and (4) evidencing behaviors that cause excess disability and are not solely attributable to another disorder (psychiatric, medical, or substance-related). A majority of the respondents rated all surveyed elements of the definition as “strongly agree” or “somewhat agree” (68–88% across elements). A majority of the respondents agreed that the definition is appropriate for clinical and research applications.
Conclusions:
A provisional consensus definition of agitation has been developed. This definition can be used to advance interventional and non-interventional research of agitation in patients with cognitive impairment.