Role of transferrin, transferrin receptors, and iron in macrophage listericidal activity.

It is not yet known what properties distinguish macrophages which can kill facultative intracellular bacteria, such as Listeria monocytogenes, from those which cannot. Listeria is an organism which requires iron for growth, yet macrophage listericidal mechanisms are also likely to be iron dependent. We show here that resident peritoneal macrophages and thioglycollate-elicited macrophages cannot kill listeria, but proteose peptone-elicited and FCS-elicited macrophages can. All these cell populations phagocytose listeria. Transferrin receptor expression is low on resident cells, intermediate on peptone- and FCS-elicited cells, and high on thioglycollate-elicited cells. Transferrin transports iron into cells via the transferrin receptor: thus, iron content of resident cells is low, of peptone- and FCS-elicited cells is intermediate, and of thioglycollate-elicited cells is high. Moreover, antibody to transferrin, which prevents it binding its receptor, inhibits listericidal macrophages from killing this bacterium. Finally, nonlistericidal cells with high transferrin receptor expression and high intracellular iron become listericidal if they are incubated with apotransferrin, an iron-free ligand which prevents iron uptake by cells. These data suggest that macrophages must have enough available intracellular iron to support listericidal mechanisms, but too much iron favors growth of the bacterium, which no longer can be killed by the macrophage

Spin dynamics of a magnetic antivortex: Micromagnetic simulations

We report on a study of the dynamics of a magnetic antivortex in a submicrometer, asteroid-shaped, permalloy ferromagnet using micromagnetic simulations. As with vortex states in disk and square geometries, a gyrotropic mode was found in which a shifted antivortex core orbits about the center of the asteroid. Pulsed magnetic fields were used to generate azimuthal or radial spin wave modes, depending on the field orientation. The degeneracy of low-frequency azimuthal mode frequencies is lifted by gyrotropic motion of the antivortex core, and restored by inserting a hole in the center of the particle to suppress this motion. We briefly compare the dynamics of the vortex state of the asteroid to the antivortex. The size dependence of the antivortex modes is reported. © 2007 The American Physical Society.published_or_final_versio

Nurse led interventions to improve control of blood pressure in people with hypertension: systematic review and meta-analysis

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.OBJECTIVE: To review trials of nurse led interventions for hypertension in primary care to clarify the evidence base, establish whether nurse prescribing is an important intervention, and identify areas requiring further study. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Ovid Medline, Cochrane Central Register of Controlled Trials, British Nursing Index, Cinahl, Embase, Database of Abstracts of Reviews of Effects, and the NHS Economic Evaluation Database. STUDY SELECTION: Randomised controlled trials of nursing interventions for hypertension compared with usual care in adults. DATA EXTRACTION: Systolic and diastolic blood pressure, percentages reaching target blood pressure, and percentages taking antihypertensive drugs. Intervention effects were calculated as relative risks or weighted mean differences, as appropriate, and sensitivity analysis by study quality was undertaken. DATA SYNTHESIS: Compared with usual care, interventions that included a stepped treatment algorithm showed greater reductions in systolic blood pressure (weighted mean difference -8.2 mm Hg, 95% confidence interval -11.5 to -4.9), nurse prescribing showed greater reductions in blood pressure (systolic -8.9 mm Hg, -12.5 to -5.3 and diastolic -4.0 mm Hg, -5.3 to -2.7), telephone monitoring showed higher achievement of blood pressure targets (relative risk 1.24, 95% confidence interval 1.08 to 1.43), and community monitoring showed greater reductions in blood pressure (weighted mean difference, systolic -4.8 mm Hg, 95% confidence interval -7.0 to -2.7 and diastolic -3.5 mm Hg, -4.5 to -2.5). CONCLUSIONS: Nurse led interventions for hypertension require an algorithm to structure care. Evidence was found of improved outcomes with nurse prescribers from non-UK healthcare settings. Good quality evidence from UK primary health care is insufficient to support widespread employment of nurses in the management of hypertension within such healthcare systems.Scientific Foundation Board of the Royal College of General PractitionersSouth West GP Trus

The difference in blood pressure readings between arms and survival: primary care cohort study

addresses: Primary Care Research Group, Institute of Health Services Research, Peninsula College of Medicine and Dentistry, University of Exeter, Devon EX1 2LU, UK. [email protected]: PMCID: PMC3309155To determine whether a difference in systolic blood pressure readings between arms can predict a reduced event free survival after 10 years

Associations between interarm differences in blood pressure and cardiovascular disease outcomes: protocol for an individual patient data meta-analysis and development of a prognostic algorithm

This is the final version of the article. Available on open access from BMJ Publishing Group via the DOI in this record.There is another record for this publication in ORE: http://hdl.handle.net/10871/32190INTRODUCTION: Individual cohort studies in various populations and study-level meta-analyses have shown interarm differences (IAD) in blood pressure to be associated with increased cardiovascular and all-cause mortality. However, key questions remain, such as follows: (1) What is the additional contribution of IAD to prognostic risk estimation for cardiovascular and all-cause mortality? (2) What is the minimum cut-off value for IAD that defines elevated risk? (3) Is there a prognostic value of IAD and do different methods of IAD measurement impact on the prognostic value of IAD? We aim to address these questions by conducting an individual patient data (IPD) meta-analysis. METHODS AND ANALYSIS: This study will identify prospective cohort studies that measured blood pressure in both arms during recruitment, and invite authors to contribute IPD datasets to this collaboration. All patient data received will be combined into a single dataset. Using one-stage meta-analysis, we will undertake multivariable time-to-event regression modelling, with the aim of developing a new prognostic model for cardiovascular risk estimation that includes IAD. We will explore variations in risk contribution of IAD across predefined population subgroups (eg, hypertensives, diabetics), establish the lower limit of IAD that is associated with additional cardiovascular risk and assess the impact of different methods of IAD measurement on risk prediction. ETHICS AND DISSEMINATION: This study will not include any patient identifiable data. Included datasets will already have ethical approval and consent from their sponsors. Findings will be presented to international conferences and published in peer reviewed journals, and we have a comprehensive dissemination strategy in place with integrated patient and public involvement. PROSPERO REGISTRATION NUMBER: CRD42015031227.National Institute for Health Research (NIHR

Exome sequencing followed by large-scale genotyping suggests a limited role for moderately rare risk factors of strong effect in schizophrenia.

Schizophrenia is a severe psychiatric disorder with strong heritability and marked heterogeneity in symptoms, course, and treatment response. There is strong interest in identifying genetic risk factors that can help to elucidate the pathophysiology and that might result in the development of improved treatments. Linkage and genome-wide association studies (GWASs) suggest that the genetic basis of schizophrenia is heterogeneous. However, it remains unclear whether the underlying genetic variants are mostly moderately rare and can be identified by the genotyping of variants observed in sequenced cases in large follow-up cohorts or whether they will typically be much rarer and therefore more effectively identified by gene-based methods that seek to combine candidate variants. Here, we consider 166 persons who have schizophrenia or schizoaffective disorder and who have had either their genomes or their exomes sequenced to high coverage. From these data, we selected 5,155 variants that were further evaluated in an independent cohort of 2,617 cases and 1,800 controls. No single variant showed a study-wide significant association in the initial or follow-up cohorts. However, we identified a number of case-specific variants, some of which might be real risk factors for schizophrenia, and these can be readily interrogated in other data sets. Our results indicate that schizophrenia risk is unlikely to be predominantly influenced by variants just outside the range detectable by GWASs. Rather, multiple rarer genetic variants must contribute substantially to the predisposition to schizophrenia, suggesting that both very large sample sizes and gene-based association tests will be required for securely identifying genetic risk factors. © 2012 The American Society of Human Genetics

Theory of first-order layering transitions in thin helium films

Journals published by the American Physical Society can be found at http://journals.aps.org/Thin liquid He-4 films on graphite show evidence of layered growth with increasing number density via a succession of first-order phase transitions. These so-called ''layering transitions'' separate uniformly covering phases, such as monolayers and bilayers. The present work is a detailed theoretical study of such layering transitions using a Maxwell construction. We model the graphite surface by a strong substrate potential, and using a microscopic variational theory we obtain the uniform coverage solutions for liquid helium. For each layer, the theory yields the chemical potential mu and surface tension alpha as functions of coverage n, and from this we deduce mu(a). For each set of adjacent layers, we then obtain the crossing point in the curves of mu(alpha). In this way we obtain the values of mu, alpha, and surface coverages for the transition. Particular attention is paid to the monolayer-bilayer transition

Vitamin D and COVID-19 in older age: evidence versus expectations

This is the author accepted manuscript. The final version is available from the Royal College of General Practitioners via the DOI in this recordThe current global pandemic of SARS-CoV-2 coronavirus infection originated in Wuhan, China, during December 2019; over 50 million cases have been diagnosed to date. Older age and comorbidity have proven to be key markers of risk for severity of COVID-19 and mortality,1,2 and residents of care homes have been proven to be at high risk. The Office for National Statistics has recorded 16 111 deaths related to COVID-19 in care home residents in England up to 20 November 2020.3 In the first wave of the pandemic, 46% of all excess deaths in England and Wales up to 7 August occurred in care homes.4 Older age is associated with increasing prevalence of vitamin D deficiency, which can affect up to 40% of care home residents.5 There is considerable overlap between the non-modifiable risk factors for severe SARS-CoV-2 infection and those associated with deficiency of vitamin D. For example, age, ethnicity, diabetes, and chronic pulmonary and cardiac diseases; in addition, there is the observed trend towards greater severity of disease in northern latitudes. While these could imply an association between reduced vitamin D levels and susceptibility to SARS-CoV-2 infection this may simply be an ecological fallacy.6 Therefore, it is important to understand the strength of evidence provided by epidemiological and observational studies of COVID-19, and compare it with what is known from clinical trials of the impact of vitamin D supplementation on acute respiratory infections, including those due to SARS-CoV-2.National Institute for Health Research (NIHR

The rural dispensing practice – better medication adherence and clinical outcomes compared to non-dispensing practices? A cross-sectional analysis of routine data

This is the author accepted manuscript. The final version is available on open access from the Royal College of General Practitioners via the DOI in this record.Background Most patients obtain medications from pharmacies by prescription, but rural general practices can dispense medications. Clinical implications of this difference in drug delivery are unknown. We hypothesised that dispensing status may be associated with better medication adherence. This could impact intermediate clinical outcomes dependent on medication adherence in, for example, hypertension or diabetes. Aim We investigated whether dispensing status is associated with differences in achievement of Quality and Outcome Framework (QOF) indicators that rely on medication adherence. Design and Setting Cross-sectional analysis of QOF data for 7,392 general practices in England. Method We analysed QOF data from 2016/17 linked to dispensing status for general practices with list sizes ≥1000 in England. QOF indicators were categorised according to whether their achievement depended on a record of prescribing only, medication adherence, or neither. We estimated differences between dispensing and non-dispensing practices using mixed-effects logistic regression adjusting for practice population age, sex, deprivation, list size, single-handed status and rurality. Results Data existed for 7,392 practices; 1,014 (13.7%) could dispense. Achievement was better in dispensing practices than in non-dispensing practices for seven of nine QOF indicators dependant on adherence, including blood pressure targets. Only one of ten indicators dependent on prescribing but not adherence displayed evidence of a difference; indicators unrelated to prescribing showed a trend towards higher achievement by dispensing practices. Conclusion Dispensing practices may achieve better clinical outcomes than prescribing practices. Further work is required to explore underlying mechanisms for these observations, and to directly study medication adherence rates.South West General Practice Trus

Seagrass can mitigate negative ocean acidification effects on calcifying algae

The ultimate effect that ocean acidification (OA) and warming will have on the physiology of calcifying algae is still largely uncertain. Responses depend on the complex interactions between seawater chemistry, global/local stressors and species-specific physiologies. There is a significant gap regarding the effect that metabolic interactions between coexisting species may have on local seawater chemistry and the concurrent effect of OA. Here, we manipulated CO2 and temperature to evaluate the physiological responses of two common photoautotrophs from shallow tropical marine coastal ecosystems in Brazil: the calcifying alga Halimeda cuneata, and the seagrass Halodule wrightii. We tested whether or not seagrass presence can influence the calcification rate of a widespread and abundant species of Halimeda under OA and warming. Our results demonstrate that under elevated CO2, the high photosynthetic rates of H. wrightii contribute to raise H. cuneata calcification more than two-fold and thus we suggest that H. cuneata populations coexisting with H. wrightii may have a higher resilience to OA conditions. This conclusion supports the more general hypothesis that, in coastal and shallow reef environments, the metabolic interactions between calcifying and non-calcifying organisms are instrumental in providing refuge against OA effects and increasing the resilience of the more OA-susceptible species.E.B. would like to thank the Coordenação de Aperfeiçoamento de Pessoas de Nível Superior (CAPES) for Masters funding. Funding for this project came from the Synergism grant (CNPq 407365/2013-3). We extend our thanks to the Brazil-based Projeto Coral Vivo and its sponsor PetroBras Ambiental for providing the Marine Mesocosm structure and experimental assistance.info:eu-repo/semantics/publishedVersio