All-Order Full-Coulomb Quantum Spectral Line-Shape Calculations.

Understanding how atoms interact with hot dense matter is essential for astrophysical and laboratory plasmas. Interactions in high-density plasmas broaden spectral lines, providing a rare window into interactions that govern, for example, radiation transport in stars. However, up to now, spectral line-shape theories employed at least one of three common approximations: second-order Taylor treatment of broadening operator, dipole-only interactions between atom and plasma, and classical treatment of perturbing electrons. In this Letter, we remove all three approximations simultaneously for the first time and test the importance for two applications: neutral hydrogen and highly ionized magnesium and oxygen. We found 15%-50% change in the spectral line widths, which are sufficient to impact applications including white-dwarf mass determination, stellar-opacity research, and laboratory plasma diagnostics.

Coronavirus disease 2019 mortality: a multivariate ecological analysis in relation to ethnicity, population density, obesity, deprivation and pollution.

BACKGROUND: There is emerging evidence about characteristics that may increase the risk of coronavirus disease 2019 (COVID-19) mortality, but they are highly correlated. METHODS: An ecological analysis was used to estimate associations between these variables and age-standardised COVID-19 mortality rates at the local authority level. RESULTS: Ethnicity, population density and overweight/obesity were all found to have strong independent associations with COVID-19 mortality, at the local authority level. DISCUSSION: This analysis provides some preliminary evidence about which variables are independently associated with COVID-19 mortality and suggests that others (deprivation and pollution) are not directly linked. It highlights the importance of multivariate analyses to understand the factors that increase vulnerability to COVID-19.

Effect of Electron Capture on Spectral Line Broadening in Hot Dense Plasmas.

Accurate calculation of spectral line broadening is important for many hot, dense plasma applications. However, calculated line widths have significantly underestimated measured widths for Δn=0 lines of Li-like ions, which is known as the isolated-line problem. In this Letter, scrutinization of the line-width derivation reveals that the commonly used expression neglects a potentially important contribution from electron-capture. Line-width calculations including this process are performed with two independent codes, both of which removed the discrepancies at temperatures below 10 eV. The revised calculations also suggest the remaining discrepancy scales more strongly with electron temperature than the atomic number as was previously suggested.

Measuring the effectiveness of catch-up MMR delivered by school nurses compared to signposting to general practice on improving MMR coverage.

BACKGROUND: This study assesses whether increased coverage of the measles, mumps and rubella (MMR) vaccination differs between areas where school nurses deliver catch-up MMR doses to adolescents in school settings, compared to signposting to general practice. METHODS: A retrospective cohort study was conducted using Child Health Information Services records within the NHS England South (South Central) commissioning boundary. The sample population included children born 1 September 2000-31 August 2001, in school year 9 during the 2014-15 academic year. RESULTS: The primary outcome findings show an increase in coverage of at least one dose of MMR by 1.6% (n = 334) in the cohort receiving catch-up MMR, compared to 0.2% (n = 12) in the cohort signposted to general practice. Over time, the difference in increase between the two cohorts was 1.4%, analysed using the chi-squared comparison of proportions test, providing strong evidence (P < 0.0001) that school nurse delivery of catch-up MMR is effective at increasing coverage. The findings also suggest that school nurse delivery of catch-up MMR may benefit Black, Asian and minority ethnic children and those from more deprived backgrounds. CONCLUSIONS: It is recommended that commissioners of school-aged immunization services incorporate the delivery of catch-up MMR doses in their contracts with school nurses.

Health inequalities, risky behaviours and protective factors in adolescents: an analysis of secondary survey data from the UK.

OBJECTIVE: Adolescents are at risk of developing detrimental health behaviours that will affect their adult health. The aim was to estimate prevalence of health risk behaviours (HRB), comparing young people (12-18 years old) in Wiltshire (UK) who are vulnerable (looked after children, special education needs and disabilities, young carers and military dependents) to those who are not vulnerable and assess whether these behaviours are associated with protective factors (e.g. friendship groups). STUDY DESIGN: Secondary analysis of cross-sectional survey data (n = 4129). METHODS: In total, 900 vulnerable young people were compared with 3229 non-vulnerable young people. Differences between the two groups were assessed using Chi-squared tests, and associations with possible protective factors were assessed using logistic regression (adjusting for confounding factors). RESULTS: Vulnerable young people have a higher prevalence of smoking tobacco (15% vs 9%, P < 0.001), using cannabis (7% vs 5%, P = 0.03) and self-harming (16% vs 9%, P < 0.001) monthly or more compared with the rest of the Wiltshire adolescent population. Whilst vulnerable young people have many shared protective factors with non-vulnerable young people, there are also differences between the two groups. CONCLUSIONS: There are shared protective factors across HRB that can build on the resilience of a young person, impacting their current and future health. Therefore, we should focus our attention on developing protective factors that promote health and well-being, not solely delivering specialist interventions targeted at specific risks. Further consideration should be given to identifying and promoting protective factors specifically for vulnerable people as they have higher levels of HRB and experience protective factors differently.

Recommended electron-impact excitation and ionization cross sections for Be I.

Analytic fits to the recommended electron-impact excitation and ionization cross sections for Be I are presented. The lowest 19 terms of configurations 2snl (n ≤ 4) and 2p 2 terms below the first ionization limit are considered. The fits are based on the accurate calculations with the convergent close coupling (CCC) method as well as the B-spline R-matrix (BSR) approach. The fitted cross sections provide rate coefficients that are believed to approximate the original data within 10% with very few exceptions. The oscillator strengths for the dipole-allowed transitions between all the considered states are calculated with the relativistic multi-configuration Dirac-Hartree-Fock (MCDHF) approach and compared with the CCC and BSR results. This comparison shows a very good agreement except for a handful of cases with likely strong cancellations.

Near-Threshold Cross Sections for Electron and Positron Impact Ionization of Atomic Hydrogen.

Using classical arguments Wannier [Phys. Rev. 90, 817 (1953)PHRVAO0031-899X10.1103/PhysRev.90.817] proposed an electron-impact ionization cross section for neutral atoms to behave as E^{1.127}, where E is the excess energy above threshold. Using similar arguments Klar [J. Phys. B 14, 4165 (1981)JPAMA40022-370010.1088/0022-3700/14/21/027] obtained E^{2.65} to be the corresponding threshold law for positron impact. Recently, Babij et al. [Phys. Rev. Lett. 120, 113401 (2018)PRLTAO0031-900710.1103/PhysRevLett.120.113401] measured near-threshold positron-impact breakup behavior to be similar to that expected for electrons. Using the convergent close-coupling method for the atomic hydrogen target, we examine cross sections at near-threshold energies for electron and positron impact. Contrary to the experiment, the calculated cross sections are found to behave differently for the two projectiles and consistently with the aforementioned threshold laws, despite the entirely quantum nature of these problems. For electron impact, the threshold behavior holds while the total electron spin asymmetry remains constant, whereas for positron scattering the threshold law holds for breakup while the positronium-formation component of the ionization cross section remains constant.

Employability and career experiences of international graduates of MSc Public Health: a mixed methods study.

OBJECTIVES: This article aims to describe the public health career experiences of international graduates of a Master of Science in Public Health (MSc PH) programme and to contribute to developing the evidence base on international public health workforce capacity development. STUDY DESIGN: A sequential mixed methods study was conducted between January 2017 and April 2017. METHODS: Ninety-seven international graduates of one UK university's MSc PH programme were invited to take part in an online survey followed by semistructured interviews, for respondents who consented to be interviewed. We computed the descriptive statistics of the quantitative data obtained, and qualitative data were thematically analysed. RESULTS: The response rate was 48.5%. Most respondents (63%) were employed by various agencies within 1 year after graduation. Others (15%) were at different stages of doctor of philosophy studies. Respondents reported enhanced roles after graduation in areas such as public health policy analysis (74%); planning, implementation and evaluation of public health interventions (74%); leadership roles (72%); and research (70%). The common perceived skills that were relevant to the respondents' present jobs were critical analysis (87%), multidisciplinary thinking (86%), demonstrating public health leadership skills (84%) and research (77%). Almost all respondents (90%) were confident in conducting research. Respondents recommended the provision of longer public health placement opportunities, elective courses on project management and advanced statistics, and 'internationalisation' of the programme's curriculum. CONCLUSIONS: The study has revealed the relevance of higher education in public health in developing the career prospects and skills of graduates. International graduates of this MSc PH programme were satisfied with the relevance and impact of the skills they acquired during their studies. The outcomes of this study can be used for curriculum reformation. Employers' perspectives of the capabilities of these graduates, however, need further consideration.

A physiologically relevant 3D collagen-based scaffold-neuroblastoma cell system exhibits chemosensitivity similar to orthotopic xenograft models.

3D scaffold-based in vitro cell culturing is a recent technological advancement in cancer research bridging the gap between conventional 2D culture and in vivo tumours. The main challenge in treating neuroblastoma, a paediatric cancer of the sympathetic nervous system, is to combat tumour metastasis and resistance to multiple chemotherapeutic drugs. The aim of this study was to establish a physiologically relevant 3D neuroblastoma tissue-engineered system and explore its therapeutic relevance. Two neuroblastoma cell lines, chemotherapeutic sensitive Kelly and chemotherapeutic resistant KellyCis83 were cultured in a 3D in vitro model on two collagen-based scaffolds containing either glycosaminoglycan (Coll-GAG) or nanohydroxyapatite (Coll-nHA) and compared to 2D cell culture and an orthotopic murine model. Both neuroblastoma cell lines actively infiltrated the scaffolds and proliferated displaying >100-fold increased resistance to cisplatin treatment when compared to 2D cultures, exhibiting chemosensitivity similar to orthotopic xenograft in vivo models. This model demonstrated its applicability to validate miRNA-based gene delivery. The efficacy of liposomes bearing miRNA mimics uptake and gene knockdown was similar in both 2D and 3D in vitro culturing models highlighting the proof-of-principle for the applicability of 3D collagen-based scaffolds cell system for validation of miRNA function. Collectively, this data shows the successful development and characterisation of a physiologically relevant, scaffold-based 3D tissue-engineered neuroblastoma cell model, strongly supporting its value in the evaluation of chemotherapeutics, targeted therapies and investigation of neuroblastoma pathogenesis. While neuroblastoma is the specific disease being focused upon, the platform may have multi-functionality beyond this tumour type. STATEMENT OF SIGNIFICANCE: Traditional 2D cell cultures do not completely capture the 3D architecture of cells and extracellular matrix contributing to a gap in our understanding of mammalian biology at the tissue level and may explain some of the discrepancies between in vitro and in vivo results. Here, we demonstrated the successful development and characterisation of a physiologically relevant, scaffold-based 3D tissue-engineered neuroblastoma cell model, strongly supporting its value in the evaluation of chemotherapeutics, targeted therapies and investigation of neuroblastoma pathogenesis. The ability to test drugs in this reproducible and controllable tissue-engineered model system will help reduce the attrition rate of the drug development process and lead to more effective and tailored therapies. Importantly, such 3D cell models help to reduce and replace animals for pre-clinical research addressing the principles of the 3Rs.

Quantum suppression of antihydrogen formation in positronium-antiproton scattering.

The interaction of antiprotons with low-energy positronium atoms is a fundamental three-body problem whose significance is its utility for formation of antihydrogen. Particular importance resides in understanding processes involving excited positronium states. Until recently such studies were performed using classical techniques. However, they become inapplicable in the low-energy domain. Here we report the results of comprehensive quantum calculations, which include initial excited positronium states with principal quantum numbers up to n i = 5. Contrary to expectation from earlier work, there are only muted increases in the cross-sections for antihydrogen formation for n i > 3. We interpret this in terms of quantum suppression of the reaction at higher angular momenta. Furthermore, the cross-sections for elastic scattering are around two orders of magnitude higher, which we attribute to the degeneracy of the positronium states. We outline some experimental consequences of our results.

Antiproton stopping power data for radiation therapy simulations.

Stopping powers of H, He, H2, and H2O targets for antiprotons have been calculated using a convergent close-coupling method. For He and H2 targets electron-electron correlations are fully accounted for using a multiconfiguration approximation. Two-electron processes are included using an independent-event model. The water molecule is described using a neon-like structure model with a pseudo-spherical potential. Results are tabulated for the purpose of Monte Carlo simulations to model antiproton transport through matter for radiation therapy.

Antihydrogen Formation via Antiproton Scattering with Excited Positronium.

Utilizing the two-center convergent close-coupling method, we find a several order of magnitude enhancement in the formation of antihydrogen via antiproton scattering with positronium in an excited state over the ground state. The effect is greatest at the lowest energies considered, which encompass those achievable in experiment. This suggests a practical approach to creating neutral antimatter for testing its interaction with gravity and for spectroscopic measurements.

Target structure-induced suppression of the ionization cross section for low-energy antiproton-molecular hydrogen collisions: theoretical confirmation.

Theoretical confirmation of the experimentally observed phenomenon [Knudsen et al., Phys. Rev. Lett. 105, 213201 (2010)] of target structure-induced suppression of the ionization cross section for low-energy antiproton-molecular hydrogen collisions is given. To this end a novel time-dependent convergent close-coupling approach to the scattering problem that accounts for all possible orientations of the molecular target, has been developed. The approach is applied to study single ionization of molecular hydrogen on the wide energy range from 1 keV to 2 MeV with a particular emphasis on low energies. Results for the orientation-averaged total single ionization cross section are compared with available experimental data and good agreement is found at low (<20 keV) and high (>90 keV) energies. A minor discrepancy is found within a small energy gap near the maximum of the cross section.

Ejection of quasi-free-electron pairs from the helium-atom ground state by single-photon absorption.

We investigate the single-photon double ionization of helium at photon energies of 440 and 800 eV. We observe doubly charged ions with close to zero momentum corresponding to electrons emitted back to back with equal energy. These slow ions are the unique fingerprint of an elusive quasifree photon double ionization mechanism predicted by Amusia et al. nearly four decades ago [J. Phys. B 8, 1248 (1975)]. It results from the nondipole part of the electromagnetic interaction. Our experimental data are supported by calculations performed using the convergent close-coupling and time-dependent close-coupling methods.

Identification of circulating microRNAs in HNF1A-MODY carriers.

AIMS/HYPOTHESIS: HNF1A-MODY is a monogenic form of diabetes caused by mutations in the HNF1A gene. Here we identify, for the first time, HNF1A-MODY-associated microRNAs (miRNAs) that can be detected in the serum of HNF1A-MODY carriers. METHODS: An miRNA array was carried out in rat INS-1 insulinoma cells inducibly expressing the common human Pro291fsinsC-HNF1A frame shift mutation. Differentially expressed miRNAs were validated by quantitative real-time PCR. Expression of miRNAs in the serum of HNF1A-MODY carriers (n = 31), MODY-negative family members (n = 10) and individuals with type 2 diabetes mellitus (n = 17) was quantified by absolute real-time PCR analysis. RESULTS: Inducible expression of Pro291fsinsC-HNF1A in INS-1 cells caused a significant upregulation of three miRNAs (miR-103, miR-224, miR-292-3p). The differential expression of two miRNAs (miR-103 and miR-224) was validated in vitro. Strongly elevated levels of miR-103 and miR-224 could be detected in the serum of HNF1A-MODY carriers compared with MODY-negative family controls. Serum levels of miR-103 distinguished HNF1A-MODY carriers from HbA1c-matched individuals with type 2 diabetes mellitus. CONCLUSIONS/INTERPRETATION: Our study demonstrates that the pathophysiology of HNF1A-MODY is associated with the overexpression of miR-103 and miR-224. Furthermore, our study demonstrates that these miRNAs can be readily detected in the serum of HNF1A-MODY carriers.

Signature of two-electron interference in angular resolved double photoionization of Mg.

The double photoionization of Mg has been studied experimentally and theoretically in a kinematic where the two photoelectrons equally share the excess energy. The observation of a symmetrized gerade amplitude, which strongly deviates from the Gaussian ansatz, is explained by a two-electron interference predicted theoretically, but never before observed experimentally. Similar to the Cooper minima in the single photoionization cross section, the effect finds its origin in the radial extent and oscillation of the target wave function.

Modulation of neuroblastoma disease pathogenesis by an extensive network of epigenetically regulated microRNAs.

MicroRNAs (miRNAs) contribute to the pathogenesis of many forms of cancer, including the pediatric cancer neuroblastoma, but the underlying mechanisms leading to altered miRNA expression are often unknown. Here, a novel integrated approach for analyzing DNA methylation coupled with miRNA and mRNA expression data sets identified 67 epigenetically regulated miRNA in neuroblastoma. A large proportion (42%) of these miRNAs was associated with poor patient survival when underexpressed in tumors. Moreover, we demonstrate that this panel of epigenetically silenced miRNAs targets a large set of genes that are overexpressed in tumors from patients with poor survival in a highly redundant manner. The genes targeted by the epigenetically regulated miRNAs are enriched for a number of biological processes, including regulation of cell differentiation. Functional studies involving ectopic overexpression of several of the epigenetically silenced miRNAs had a negative impact on neuroblastoma cell viability, providing further support to the concept that inactivation of these miRNAs is important for neuroblastoma disease pathogenesis. One locus, miR-340, induced either differentiation or apoptosis in a cell context dependent manner, indicating a tumor suppressive function for this miRNA. Intriguingly, it was determined that miR-340 is upregulated by demethylation of an upstream genomic region that occurs during the process of neuroblastoma cell differentiation induced by all-trans retinoic acid (ATRA). Further biological studies of miR-340 revealed that it directly represses the SOX2 transcription factor by targeting of its 3'-untranslated region, explaining the mechanism by which SOX2 is downregulated by ATRA. Although SOX2 contributes to the maintenance of stem cells in an undifferentiated state, we demonstrate that miR-340-mediated downregulation of SOX2 is not required for ATRA induced differentiation to occur. In summary, our results exemplify the dynamic nature of the miRNA epigenome and identify a remarkable network of miRNA/mRNA interactions that significantly contribute to neuroblastoma disease pathogenesis.

MicroRNA-204 increases sensitivity of neuroblastoma cells to cisplatin and is associated with a favourable clinical outcome.

BACKGROUND: Neuroblastoma remains a major cause of cancer-linked mortality in children. miR-204 has been used in microRNA expression signatures predictive of neuroblastoma patient survival. The aim of this study was to explore the independent association of miR-204 with survival in a neuroblastoma cohort, and to investigate the phenotypic effects mediated by miR-204 expression in neuroblastoma. METHODS: Neuroblastoma cell lines were transiently transfected with miR-204 mimics and assessed for cell viability using MTS assays. Apoptosis levels in cell lines were evaluated by FACS analysis of Annexin V-/propidium iodide-stained cells transfected with miR-204 mimics and treated with chemotherapy drug or vehicle control. Potential targets of miR-204 were validated using luciferase reporter assays. RESULTS: miR-204 expression in primary neuroblastoma tumours was predictive of patient event-free and overall survival, independent of established known risk factors. Ectopic miR-204 expression significantly increased sensitivity to cisplatin and etoposide in vitro. miR-204 direct targeting of the 3' UTR of BCL2 and NTRK2 (TrkB) was confirmed. CONCLUSION: miR-204 is a novel predictor of outcome in neuroblastoma, functioning, at least in part, through increasing sensitivity to cisplatin by direct targeting and downregulation of anti-apoptotic BCL2. miR-204 also targets full-length NTRK2, a potent oncogene involved with chemotherapy drug resistance in neuroblastoma.

MicroRNAs 10a and 10b are potent inducers of neuroblastoma cell differentiation through targeting of nuclear receptor corepressor 2.

MicroRNAs function as negative regulators of posttranscriptional gene expression, having major roles in cellular differentiation. Several neuroblastoma cell lines can be induced to undergo differentiation by all-trans-retinoic acid (ATRA) and are used for modeling signaling pathways involved in this process. To identify miRNAs contributing to differentiation, we profiled 364 loci following ATRA treatment of neuroblastoma cell lines and found miR-10a and miR-10b to be highly overexpressed in SK-N-BE, LAN5 and SHSY-5Y. Ectopic overexpression of these miRNAs led to a major reprogramming of the transcriptome and a differentiated phenotype that was similar to that induced by ATRA in each of these cell lines. One of the predicted downregulated miR-10a/b targets was nuclear receptor corepressor 2 (NCOR2), a corepressor of gene transcription, which is known to suppress neurite outgrowth. NCOR2 was experimentally validated as a direct target of miR-10a/b, and siRNA-mediated inhibition of this mRNA alone resulted in neural cell differentiation. Moreover, induction of differentiation could be blocked by ectopic upregulation of NCOR2 using an expression construct lacking the miR-10a/b 3' untranslated region target site. We conclude that miR-10a/b has major roles in the process of neural cell differentiation through direct targeting of NCOR2, which in turn induces a cascade of primary and secondary transcriptional alterations, including the downregulation of MYCN.

Physical mechanisms and scaling laws of K-shell double photoionization.

We report on the photon energy dependence of the K-shell double photoionization (DPI) of Mg, Al, and Si. The DPI cross sections were derived from high-resolution measurements of x-ray spectra following the radiative decay of the K-shell double vacancy states. Our data evince the relative importance of the final-state electron-electron interaction to the DPI. By comparing the double-to-single K-shell photoionization cross-section ratios for neutral atoms with convergent close-coupling calculations for He-like ions, the effect of outer shell electrons on the K-shell DPI process is assessed. Universal scaling of the DPI cross sections with the effective nuclear charge for neutral atoms is revealed.