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In this work, we discuss the challenges related to the preliminary investigation of high repetition rate (HRR) experiments in the field of high energy density (HED) physics, and we present the results of preparation experiments done at the Prague Asterix Laser System (PALS) laser facility conducted with the aim of defining the needed developments in target design, real-time diagnostics and data collection needed to meet HRR requirements. Although the PALS laser facility is not an HRR facility, it has served as a valuable test bed for advancing diagnostic techniques and refining target design in preparation for HRR experimental platforms. HRR operation will result in improved statistical errors of the experimental results, in particular for experiments related to equation of state studies in extreme conditions.
The generation of intense radio-frequency and microwave electromagnetic pulses (EMPs) by the interaction of a high-power laser with a target is an interesting phenomenon, the exact mechanisms of which remain inadequately explained. In this paper we present a detailed characterization of the EMP emission at a sub-nanosecond kilojoule laser facility, the Prague Asterix Laser System. The EMPs were detected using a comprehensive set of broadband diagnostics including B-dot and D-dot probes, various antennas, target current and voltage probes and oscilloscopes with 100 and 128 GS/s sampling. Measurements show that the EMP spectrum was strongly dependent on the laser energy: the maximum frequency of the spectrum and the frequency of the spectrum centroid increased with increasing laser beam energy in the signals from all detectors used. The highest observed frequencies exceeded 9 GHz. The amplitude and energy of the detected EMP signals were scaled as a function of laser energy, power and number of emitted electrons.
This study investigated the psychometric properties of the Highly Sensitive Child-Rating System (HSC-RS), the existence of sensitivity groups, and the characterization of sensitivity at behavioral, genetic, and physiological levels in 541 preschoolers (M(SD)age = 3.56(0.27); 45%male; 87%Caucasian). Temperament, genetic, cortisol, and electroencephalography asymmetry data were collected in subsamples (n = 94-476). Results showed a reliable observational measure of sensitivity. Confirmatory factor and latent class analysis supported a one-factor solution and three sensitivity groups, that are a low (23.3%), medium (54.2%), and a high (22.5%) sensitivity group. Hierarchical regression analyses showed moderate associations between HSC-RS and observed temperament traits (i.e., behavioral level). In addition, a small negative association between HSC-RS and a genome-wide association study polygenic risk score (GWAS PGS) for Attention Deficit Hyperactivity Disorder was found. No relations with candidate genes, other GWAS PGS phenotypes, and physiological measures were found. Implications of our findings and possible explanations for a lack of these associations are discussed.
In 2021, approximately 15,000 men in Germany died from prostate cancer (PCa). The national health policy is considering shifting from annual digital rectal examination (DRE)-based screening to an age-related prostate-specific antigen (PSA)-based risk-adapted and organized screening strategy. Our research investigated the cost–utility of the current DRE-based strategy versus organized age-related PSA-based risk-adaptive PCa screening strategies in Germany.
Methods
We adapted the Swedish Prostata model to the German context, recalibrating it with PCa clinical and epidemiological data from the national and state registries. The model includes preclinical and clinical disease health states defined by tumor, nodal, and metastatic stages and Gleason scores, and assumes that the benefits of screening arise from stage shift. We assessed the cost–utility of 14 strategies, ranging from no screening to DRE, and age-related, PSA-based, risk-adapted screening. Health state utility values and test characteristics were sourced from the literature. Inpatient and outpatient care costs were derived from the German diagnostic-related groups and uniform-based valuation systems.
Results
Among all strategies evaluated and compared with no screening, the “DRE only” strategy led to substantial overdiagnosis, the highest incremental cost, and minimal quality-adjusted life years (QALY) gains. PSA testing starting at 50 to 60 years with reflex MRI for PSA greater than 3 ng/mL cases followed by combined systemic and targeted biopsy reduced the number of biopsies and overdiagnosis by 75 percent and 26 percent, albeit for fewer QALYs and higher costs (dominated) than the same strategy without reflex MRI. The PSA-based risk-adaptive strategy, starting at 50 to 60 years without reflex MRI, demonstrated an 85 percent probability of being cost effective within the EUR30,000 (USD32,211) to EUR100,000 (USD107,369)/QALY willingness-to-pay range.
Conclusions
While Germany’s HTA emphasizes clinically added benefits and health-related quality of life, cost-effectiveness analysis substantiates this evidence. As a standalone early detection tool, DRE leads to substantial overdiagnosis, unnecessary biopsies, and increased healthcare costs. Overall, this study demonstrated the importance of age-related PSA risk-adaptive PCa screening. The value of MRI deserves further investigation, considering MRI’s positive effect on screening acceptability.
A volatile environment and an increasing number of products along with a growing range of functions pose a challenge for companies when it comes to further development. Existing methods are no longer sufficient to cope with these challenges. In order to develop new methods, the process and challenges in the advancement of product portfolios must be understood. In this paper we conduct an interview study with ten experts to gain a better understanding of the advancement of product portfolios. Triggers, changes and actions are examined and goals and requirements for new methods are derived.
The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.
At the time of this meeting, the latest Gaia data release is EDR3, published on 3 December 2020, but the next one, DR3, will appear soon, on 13 June 2022. This contribution describes, on the one hand, Gaia EDR3 results on massive stars and young stellar clusters, placing special emphasis on how a correct treatment of the astrometric and photometric calibration yields results that are simultaneously precise and accurate. On the other hand, it gives a brief description of the exciting results we can expect from Gaia DR3.
In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.
We investigate a theoretical framework for modelling fluid turbulence based on the formalism of exact coherent structures (ECSs). Although highly promising, existing evidence for the role of ECSs in turbulent flows is largely circumstantial and comes primarily from idealized numerical simulations. In particular, it remains unclear whether three-dimensional turbulent flows in experiment shadow any ECSs. In order to conclusively answer this question, a hierarchy of ECSs should be computed on a domain and with boundary conditions exactly matching experiment. The present study makes the first step in this direction by investigating a small-aspect-ratio Taylor–Couette flow with naturally periodic boundary conditions in the azimuthal direction. We describe the structure of the chaotic set underlying turbulent flow driven by counter-rotating cylinders and present direct numerical evidence for shadowing of a collection of unstable relative periodic orbits and a travelling wave, setting the stage for further experimental tests of the framework.
We construct a mirabolic analogue of the geometric Satake equivalence. We also prove an equivalence that relates representations of a supergroup to the category of $\operatorname{GL}(N-1,{\mathbb {C}}[\![t]\!])$-equivariant perverse sheaves on the affine Grassmannian of $\operatorname{GL}_N$. We explain how our equivalences fit into a more general framework of conjectures due to Gaiotto and to Ben-Zvi, Sakellaridis and Venkatesh.
Alaska's largest city, Anchorage, depends on Eklutna Glacier meltwater for drinking water and hydropower generation; however, the 29 km2 glacier is rapidly retreating. We used a temperature-index model forced with local weather station data to reconstruct the glacier's mass balance for the period 1985–2019 and quantify the impacts of glacier change on discharge. Model calibration involved a novel combination of in situ, geodetic mass-balance measurements and observed snowlines from satellite imagery. A resulting ensemble of 250 best-fitting model parameters was used to model mass balance and discharge. Eklutna Glacier experienced a significant negative trend (−0.31 m w.e. decade−1) in annual mean surface mass balance (mean: −0.62 ± 0.06 m w.e.). The day of the year when 95% of annual melt occurs was five days later in 2011–19 than in 1985–93, demonstrating a prolongation of melt season (May–September). Modeled mean specific discharge increased at 0.14 m decade−1, indicating peak water, the year when annual discharge reaches a maximum due to glacier retreat, has not been reached. Four of the five highest discharge years occurred since 2000. Increases in discharge quantity and melt season length require water resource managers consider future decreased discharge as the glacier continues to shrink.
The logarithmic helicospiral has been the most widely accepted model of regularly coiled molluscan form since it was proposed by Moseley and popularized by Thompson and Raup. It is based on an explicit assumption that shells are isometric and grow exponentially, and an implicit assumption that the external form of the shell follows the internal shape, which implies that the parameters of the spiral could be reconstructed from the external whorl profile. In this contribution, we show that these assumptions fail on all 25 gastropod species we examine. Using a dataset of 176 fossil and modern gastropod shells, we construct an empirical morphospace of coiling using the parameters of whorl expansion rate, translation rate, and rate of increasing distance from coiling axis, plus rate of aperture shape change, from their best-fit models. We present a case study of change in shell form through geologic time in the austral family Struthiolariidae to demonstrate the utility of our approach for evolutionary paleobiology. We fit various functions to the shell-coiling parameters to demonstrate that the best morphological model is not the same for each parameter. We present a set of R routines that will calculate helicospiral parameters from sagittal sections through coiled shells and allow workers to compare models and choose appropriate sets of parameters for their own datasets. Shell-form parameters in the Struthiolariidae highlight a hitherto neglected hypothesis of relationship between Antarctic Perissodonta and the enigmatic Australian genus Tylospira that fits the biogeographic and stratigraphic distribution of both genera.
The diversity and biology of Cryptosporidium that is specific for rats (Rattus spp.) are not well studied. We examined the occurrence and genetic diversity of Cryptosporidium spp. in wild brown rats (Rattus norvegicus) by microscopy and polymerase chain reaction (PCR)/sequencing targeting the small subunit rDNA (SSU), actin and HSP70 genes. Out of 343 faecal samples tested, none were positive by microscopy and 55 were positive by PCR. Sequence analysis of SSU gene revealed the presence of Cryptosporidium muris (n = 4), C. andersoni (n = 3), C. ryanae (n = 1), C. occultus (n = 3), Cryptosporidium rat genotype I (n = 23), Cryptosporidium rat genotype IV (n = 16) and novel Cryptosporidium rat genotype V (n = 5). Spherical oocysts of Cryptosporidium rat genotype I obtained from naturally-infected rats, measuring 4.4–5.4 μm × 4.3–5.1 μm, were infectious to the laboratory rats, but not to the BALB/c mice (Mus musculus) nor Mongolian gerbils (Meriones unguiculatus). The prepatent period was 3 days post infection and the patent period was longer than 30 days. Naturally- and experimentally-infected rats showed no clinical signs of disease. Percentage of nucleotide similarities at the SSU, actin, HSP70 loci between C. ratti n. sp. and the rat derived C. occultus and Cryptosporidium rat genotype II, III, IV, and V ranged from 91.0 to 98.1%. These genetic variations were similar or greater than that observed between closely related species, i.e. C. parvum and C. erinacei (93.2–99.5%). Our morphological, genetic and biological data support the establishment of Cryptosporidium rat genotype I as a new species, Cryptosporidium ratti n. sp.
The transition to turbulence in Taylor–Couette flow often occurs via a sequence of supercritical bifurcations to progressively more complex, yet stable, flows. We describe a subcritical laminar–turbulent transition in the counter-rotating regime mediated by a transient intermediate state in a system with an axial aspect ratio of $\unicode[STIX]{x1D6E4}=5.26$ and a radius ratio of $\unicode[STIX]{x1D702}=0.905$. In this regime, flow visualization experiments and numerical simulations indicate the intermediate state corresponds to an aperiodic flow featuring interpenetrating spirals. Furthermore, the reverse transition out of turbulence leads first to the same intermediate state, which is now stable, before returning to an azimuthally symmetric laminar flow. Time-resolved tomographic particle image velocimetry is used to characterize the experimental flows; these measurements compare favourably to direct numerical simulations with axial boundary conditions matching those of the experiments.
The Accountability for Reasonableness (A4R) framework addresses the legitimacy of coverage decision processes by defining four conditions for accountable and reasonable processes: Relevance, Publicity, Appeals, Implementation. Cost-per-quality-adjusted life year (QALY) and multicriteria-centered processes may have distinct implications for meeting A4R conditions. The aim of this study was to reflect on how the diverse features of decision-making processes can be aligned with A4R conditions to guide legitimized decision-making. Rare disease and regenerative therapies (RDRTs) pose special decision-making challenges and offer a useful case study.
Methods:
To support reflection on how different approaches address the A4R conditions, thirty-four features operationalizing each condition were defined and organized into a matrix. Seven experts from six countries explored and discussed these features during a panel (Chatham House Rule) and provided general and RDRT-specific recommendations for each feature. Responses were analyzed to identify converging and diverging recommendations.
Results:
Regarding Relevance, panelists highlighted the importance of supporting deliberation, stakeholder participation and grounding coverage decision criteria in the legal framework, goals of sustainable healthcare and population values. Among seventeen criteria, thirteen were recommended by more than half of panelists. Although the cost-effectiveness ratio was deemed sometimes useful, the validity of universal thresholds to inform allocative efficiency was challenged. Regarding Publicity, panelists recommended communicating the values underlying a decision in reference to broader societal objectives, and being transparent about value judgements in selecting evidence. For Appeals, recommendations included clear definition of new evidence and revision rules. For Implementation, one recommendation was to perform external quality reviews of decisions. While RDRTs raise issues that may warrant special consideration, rarity should be considered in interaction with other aspects (e.g. disease severity, age, budget impact).
Conclusions:
Improving coverage decision-making towards accountability and reasonableness involves supporting participation and deliberation, enhancing transparency, and more explicit consideration of multiple decision criteria that reflect normative and societal objectives.
Traditional perspectives conceptualize resilience as a trait and depression as resulting from resilience deficiency. However, research indicates that resilience varies substantially even among adults who are clinically depressed, as well as across the lifespan of an individual. Few studies have investigated resilience in depression, and even fewer have examined resilience in depressed older adults.
Methods:
Three hundred thirty-seven adults ≥60 years with major depressive disorder completed the Connor–Davidson Resilience Scale (CD-RISC) and measures of mental health, quality of life (QOL), and medical comorbidity. Exploratory factor analysis was used to explore the factor structure of the CD-RISC. Correlations and general linear models were used to examine associations between resilience and other variables.
Results:
The rotated component matrix indicated a four-factor model. Sorting of items by highest factor loading revealed constructs associated with (1) grit, (2) active coping self-efficacy, (3) accommodative coping self-efficacy, and (4) spirituality. Resilience was significantly correlated with increased age, lower cognitive functioning, greater cerebrovascular risk, and greater medical comorbidity. Resilience was negatively associated with mental health symptoms (depression, apathy, and anxiety) and positively associated with QOL. The final optimal model identified less depression, less apathy, greater medical comorbidity, higher QOL, and minority (non-White) race as factors that significantly explained variability in resilience.
Conclusions:
Resilience was significantly associated with a range of mental health constructs in a sample of older adults with depression. Future clinical trials and dismantling studies may help determine whether interventions targeting grit, active coping, accommodative coping, and spirituality can increase resilience and help prevent and treat depression in older adults.
We present a combined experimental and theoretical study of the primary and secondary instabilities in a Kolmogorov-like flow. The experiment uses electromagnetic forcing with an approximately sinusoidal spatial profile to drive a quasi-two-dimensional (Q2D) shear flow in a thin layer of electrolyte suspended on a thin lubricating layer of a dielectric fluid. Theoretical analysis is based on a two-dimensional (2D) model (Suri et al., Phys. Fluids, vol. 26 (5), 2014, 053601), derived from first principles by depth-averaging the full three-dimensional Navier–Stokes equations. As the strength of the forcing is increased, the Q2D flow in the experiment undergoes a series of bifurcations, which is compared with results from direct numerical simulations of the 2D model. The effects of confinement and the forcing profile are studied by performing simulations that assume spatial periodicity and strictly sinusoidal forcing, as well as simulations with realistic no-slip boundary conditions and an experimentally validated forcing profile. We find that only the simulation subject to physical no-slip boundary conditions and a realistic forcing profile provides close, quantitative agreement with the experiment. Our analysis offers additional validation of the 2D model as well as a demonstration of the importance of properly modelling the forcing and boundary conditions.