First principles calculation of uniaxial magnetic anisotropy and magnetostriction in strained CMR films

We performed first - principles relativistic full-potential linearized augmented plane wave calculations for strained tetragonal ferromagnetic La(Ba)MnO$_3$ with an assumed experimental structure of thin strained tetragonal La$_{0.67}$Ca$_{0.33}$MnO$_3$ (LCMO) films grown on SrTiO$_3$[001] and LaAlO$_3$[001] substrates. The calculated uniaxial magnetic anisotropy energy (MAE) values, are in good quantitative agreement with experiment for LCMO films on SrTiO$_3$ substrate. We also analyze the applicability of linear magnetoelastic theory for describing the stain dependence of MAE, and estimate magnetostriction coefficient $\lambda_{001}$.Comment: Talk given at APS99 Meeting, Atlanta, 199

The Dipion Mass Spectrum In e+e- Annihilation and tau Decay: A Dynamical (rho0, omega, phi) Mixing Approach

We readdress the problem of finding a simultaneous description of the pion form factor data in e+e- annihilations and in tau decays. For this purpose, we work in the framework of the Hidden Local Symmetry (HLS) Lagrangian and modify the vector meson mass term by including the pion and kaon loop contributions. This leads us to define the physical rho, omega and phi fields as linear combinations of their ideal partners, with coefficients being meromorphic functions of s, the square of the 4--momentum flowing into the vector meson lines. This allows us to define a dynamical, i.e. s-dependent, vector meson mixing scheme. The model is overconstrained by extending the framework in order to include the description of all meson radiative (V P gamma and P gamma gamma couplings) and leptonic (Ve+e- couplings) decays and also the isospin breaking (omega/ phi --> pi+ pi-) decay modes. The model provides a simultaneous, consistent and good description of the e+e- and tau dipion spectra. The expression for pion form factor in the latter case is derived from those in the former case by switching off the isospin breaking effects specific to e+e- and switching on those for tau decays. Besides, the model also provides a good account of all decay modes of the form V P gamma, Pgamma gamma as well as the isospin breaking decay modes. It leads us to propose new reference values for the rho^0 --> e+ e- and omega --> pi+ pi- partial widths which are part of our description of the pion form factor. Other topics (phi --> K anti K, the rho meson mass and width parameters) are briefly discussed. Therefore, we confirm the 3.3 sigma discrepancy between the theoretical estimate of a_mu based on e+e- and its direct BNL measurement.Comment: 71 pages, 8 figures. Accepted by EPJ C. Version 3: correct minor typos, minor changes spread out into the text. Extension of Sections 12.2 and 12.3.5 and introduction of the new Appendix

Familial thrombocytopenia due to a complex structural variant resulting in a WAC-ANKRD26 fusion transcript

Advances in genome sequencing have resulted in the identification of the causes for numerous rare diseases. However, many cases remain unsolved with standard molecular analyses. We describe a family presenting with a phenotype resembling inherited thrombocytopenia 2 (THC2). THC2 is generally caused by single nucleotide variants that prevent silencing of ANKRD26 expression during hematopoietic differentiation. Short-read whole-exome and genome sequencing approaches were unable to identify a causal variant in this family. Using long-read whole-genome sequencing, a large complex structural variant involving a paired-duplication inversion was identified. Through functional studies, we show that this structural variant results in a pathogenic gain-of-function WAC-ANKRD26 fusion transcript. Our findings illustrate how complex structural variants that may be missed by conventional genome sequencing approaches can cause human disease

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

Accelarated immune ageing is associated with COVID-19 disease severity

Background The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. Results We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ( = 0.174, p = 0.043), with a major influence being disease severity ( = 0.188, p = 0.01). Conclusions Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease

Medication use and lung function among asthmatics seen in an outpatient chest clinic in Addis Ababa, Ethiopia -A needs assessment

Introduction: Asthma is significant in Ethiopia and appropriate treatment has been inconsistent. We evaluated lung function and medication use among asthmatics seen in the outpatient chest clinic of Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia.Methods: A cross-sectional study was conducted from July 1 to December 30, 2015. Chart review was used to obtain clinical information and spirometric values on those with physician-diagnosed asthma. Airflow obstruction was defined as a FEV1/FVC &lt; 70% and an FEV1&lt; 80% predicted.Results: 96 study subjects were identified. The mean age was 53 ± 12 years; 64.6% (n=62) were female. Twenty-five percent (n=24) had normal spirometry and 75% (n=72) had airflow obstruction. In multivariate analysis, impaired lung function was associated with longer duration of asthma (adjusted OR 3.89, 95% CI 1.24–12.24) and an asthma exacerbation in the last 12 months (adjusted OR 3.38, 95% CI 1.11–10.30). Of those 72 asthmatics with impaired lung function, 94.4% (n=68) were using SABA but only 56% (n=40) were on ICS.Conclusion: Most study asthmatics had impaired lung function and were not on appropriate asthma treatment. These findings suggest a need for more readily available and inexpensive asthma medications as well as qualified physicians to guide asthma management in Ethiopia

Ensuring planetary survival: the centrality of organic carbon in balancing the multifunctional nature of soils

Not only do soils provide 98.7% of the calories consumed by humans, they also provide numerous other functions upon which planetary survivability closely depends. However, our continuously increasing focus on soils for biomass provision (food, fiber, and energy) through intensive agriculture is rapidly degrading soils and diminishing their capacity to deliver other vital functions. These tradeoffs in soil functionality – the increased provision of one function at the expense of other critical planetary functions – are the focus of this review. We examine how land-use change for biomass provision has decreased the ability of soils to regulate the carbon pool and thereby contribute profoundly to climate change, to cycle the nutrients that sustain plant growth and ecosystem health, to protect the soil biodiversity upon which many other functions depend, and to cycle the Earth’s freshwater supplies. We also examine how this decreasing ability of soil to provide these other functions can be halted and reversed. Despite the complexity and the interconnectedness of soil functions, we show that soil organic carbon plays a central role and is a master indicator for soil functioning and that we require a better understanding of the factors controlling the behavior and persistence of C in soils. Given the threats facing humanity and their economies, it is imperative that we recognize that Soil Security is itself an existential challenge and that we need to increase our focus on the multiple functions of soils for long-term human welfare and survivability of the planet