Systematic and variational truncation of the configuration space in the multiconfiguration time-dependent Hartree method: The MCTDH[n] hierarchy

The multiconfiguration time-dependent Hartree (MCTDH) method is a powerful method for solving the time-dependent Schrödinger equation in quantum molecular dynamics. It is, however, hampered by the so-called curse of dimensionality which results in exponential scaling with respect to the number of degrees of freedom in the system and, thus, limits its applicability to small- and medium-sized molecules. To avoid this scaling, we derive equations of motion for a series of truncated MCTDH methods using a many-mode second-quantization formulation where the configuration space is restricted based on mode-combination levels as also done in the vibrational configuration interaction and vibrational coupled cluster methods for solving the time-independent Schrödinger equation. The full MCTDH wave function is invariant with respect to the choice of constraint (or gauge) operators, but restricting the configuration space removes this invariance. We, thus, analyze the remaining redundancies and derive equations for variationally optimizing the non-redundant matrix elements of the constraint operators. As an alternative, we also present a constraint that keeps the density matrices block diagonal during the propagation and the two choices are compared. Example calculations are performed on formyl fluoride and a series of high-dimensional Henon–Heiles potentials. The results show that the MCTDH[n] methods can be applied to large systems and that an optimal choice of constraint operators is key to obtaining the correct physical behavior of the wave function

Contemporary medical television and crisis in the NHS

This article maps the terrain of contemporary UK medical television, paying particular attention to Call the Midwife as its centrepiece, and situating it in contextual relation to the current crisis in the NHS. It provides a historical overview of UK and US medical television, illustrating how medical television today has been shaped by noteworthy antecedents. It argues that crisis rhetoric surrounding healthcare leading up to the passing of the Health and Social Care Act 2012 has been accompanied by a renaissance in medical television. And that issues, strands and clusters have emerged in forms, registers and modes with noticeable regularity, especially around the value of affective labour, the cultural politics of nostalgia and the neoliberalisation of healthcare

Introduction: Pluriversalisty, Convergence and Hybridity in the Global Left

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this recor

Guidelines (1988) for training in clinical laboratory management

Trainees in laboratory medicine must develop skills in laboratory management. Guidelines are detailed for laboratory staff in training, directors responsible for staff development and professional bodies wishing to generate material appropriate to their needs. The syllabus delineates the knowledge base required and includes laboratory planning and organization, control of operations, methodology and instrumentation, data management and statistics, financial management, clinical use of tests, communication, personnel management and training and research and development. Methods for achievement of the skills required are suggested. A bibliography of IFCC publications and other material is provided to assist in training in laboratory management

Methods for reliability and uncertainty assessment and for applicability evaluations of classification- and regression-based QSARs

This article provides an overview of methods for reliability assessment of quantitative structure–activity relationship (QSAR) models in the context of regulatory acceptance of human health and environmental QSARs. Useful diagnostic tools and data analytical approaches are highlighted and exemplified. Particular emphasis is given to the question of how to define the applicability borders of a QSAR and how to estimate parameter and prediction uncertainty. The article ends with a discussion regarding QSAR acceptability criteria. This discussion contains a list of recommended acceptability criteria, and we give reference values for important QSAR performance statistics. Finally, we emphasize that rigorous and independent validation of QSARs is an essential step toward their regulatory acceptance and implementation. Key words: QSAR acceptability criteria, QSAR applicability domain, QSAR reliability, QSAR uncertainty estimation, QSAR validation

Development of coordination and muscular fitness in children and adolescents with parent-reported ADHD in the German longitudinal MoMo Study

This study examined the development of muscular fitness and coordination in children and adolescents with and without attention deficit hyperactivity disorder (ADHD) over a period of 11 years. Data was collected in three measurement waves as part of the longitudinal, representative Motorik-Modul (MoMo) study in Germany (2003–2006, 2009–2012, 2014–2017). The overall sample comprised 2988 participants (253 with ADHD, 65% males; 2735 non-ADHD, 47% males; mean age 9 years). Structural equation modeling was conducted, and the estimated models had a good fit. No differences in muscular fitness were observed between participants with and without ADHD. Participants with ADHD had a lower coordinative performance at first measurement than those without ADHD. The difference in coordinative performance persisted throughout the study period

Patient and Public involvement in research From tokenistic box ticking to valued team members

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background Patient and public involvement (PPI) in research envisages a relationship built throughout the lifespan of a research project between academics, clinicians and PPI colleagues in order to inform, plan, execute and, in due course, disseminate and translate research. To be meaningful, all stakeholders need to actively engage in this exchange of expertise. However, despite some funders requiring PPI plans to be included in grant applications, there remains a gap between what is expected and what is delivered. Main body As an exemplar, we reflect on how, in the Asthma UK Centre for Applied Research (AUKCAR), we set out to create a supportive, organised environment with the overarching value of ‘keeping patients at the heart of everything we do’. The key has been in planning and creating a suitably funded organisational infrastructure with dedicated PPI researchers along with the development of and expectation to abide by an agreed set of norms and values. Specifically, expecting AUKCAR PhD students and early career researchers to engage with PPI has established a working mode that we hope will last. Regular interactions and proactive Patient Leads increase PPI network cohesion. Conclusion With adaptation, the AUKCAR PPI model can be translated to international contexts.TJ is the Patient and Public Involvement research fellow for the Asthma UK Centre for Applied Research and the NIHR Global Health Research Unit on Respiratory Health (RESPIRE). TJ is part funded by Asthma UK as part of the Asthma UK Centre for Applied Research (AUK-AC-2018-01). RESPIRE is funded by the National Institute for Health Research (NIHR) (16/136/109) using UK aid from the UK Government to support global health researc

Iron Homeostasis during Cystic Fibrosis Pulmonary Exacerbation

BACKGROUND: Hypoferremia is a marker of disease severity in cystic fibrosis (CF). The effect of systemic antibiotics on iron homeostasis during CF pulmonary exacerbation (CFPE) is unknown. Our central hypotheses were that, by the completion of treatment, serum iron would increase, serum concentrations of interleukin-6 (IL-6) and hepcidin-25, two mediators of hypoferremia, would decrease, and sputum iron would decrease. METHODS: Blood and sputum samples were collected from 12 subjects with moderate-to-severe CF (median percentage-predicted forced expiratory volume in 1 second (FEV(1) %) = 29%; median weight = 56 kg) within 24 hours of starting and completing a course of systemic antibiotics. RESULTS: After treatment, subjects showed median FEV(1) % and body weight improvements of 4.5% and 2.0 kg, respectively (p \u3c 0.05). Median serum iron rose by 2.4 μmol/L (p \u3c 0.05), but 75% of patients remained hypoferremic. Median serum IL-6 and hepcidin-25 levels fell by 12.1 pg/mL and 37.5 ng/mL, respectively (p \u3c 0.05). Median serum erythropoietin (EPO) and hemoglobin levels were unaffected by treatment. We observed a trend toward lower sputum iron content after treatment. CONCLUSIONS: Hypoferremia is a salient characteristic of CFPE that improves with waning inflammation. Despite antibiotic treatment, many patients remain hypoferremic and anemic because of ineffective erythropoiesis

The challenge of reconciling bottom-up agricultural methane emissions inventories with top-down measurements

Agriculture is estimated to produce more than 40% of anthropogenic methane (CH4) emissions, contributing to global climate change. Bottom-up, IPCC based methodologies are typically used to estimate the agriculture sector\u2019s contribution, but these estimates are rarely verified beyond the farm gate, due to the challenge of separating interspersed sources. We present flux measurements of CH4, using eddy covariance (EC), relaxed eddy accumulation (REA) and wavelet covariance obtained using an aircraft-based measurement platform and compare these top-down estimates with bottom-up footprint adjusted inventory estimates of CH4 emissions for an agricultural region in eastern Ontario, Canada. Top-down CH4 fluxes agree well (mean \ub1 1 standard error: EC = 17 \ub1 4 mg CH4 m 122 d 121; REA = 19 \ub1 3 mg CH4 m 122 d 121, wavelet covariance = 16 \ub1 3 mg CH4 m 122 d 121), and are not statistically different, but significantly exceed bottom-up inventory estimates of CH4 emissions based on animal husbandry (8 \ub1 1 mg CH4 m 122 d 121). The discrepancy between top-down and bottom-up estimates was found to be related to both increasing fractional area of wetlands in the flux footprint, and increasing surface temperature. For the case when the wetland area in the flux footprint was less than 10% fractional coverage, the top-down and bottom-up estimates were within the measurement error. This result provides the first independent verification of agricultural methane emissions inventories at the regional scale. Wavelet analysis, which provides spatially resolved fluxes, was used to attempt to separate CH4 emissions from managed and unmanaged CH4 sources. Opportunities to minimize the challenges of verifying agricultural CH4 emissions inventories using aircraft flux measuring systems are discussed.Peer reviewed: YesNRC publication: Ye