Misdiagnosing Melioidosis

Melioidosis is endemic in southern and Southeast Asia and northern Australia. Although relatively few indigenous cases are recognized in the Indian subcontinent, a substantial proportion of cases imported into the United Kingdom originate there, probably reflecting patterns of immigration and travel, and underdiagnosis within the Indian subcontinent

Cortical Tension Allocates the First Inner Cells of the Mammalian Embryo

Every cell in our body originates from the pluripotent inner mass of the embryo, yet it is unknown how biomechanical forces allocate inner cells in vivo. Here we discover subcellular heterogeneities in tensile forces, generated by actomyosin cortical networks, which drive apical constriction to position the first inner cells of living mouse embryos. Myosin II accumulates specifically around constricting cells, and its disruption dysregulates constriction and cell fate. Laser ablations of actomyosin networks reveal that constricting cells have higher cortical tension, generate tension anisotropies and morphological changes in adjacent regions of neighboring cells, and require their neighbors to coordinate their own changes in shape. Thus, tensile forces determine the first spatial segregation of cells during mammalian development. We propose that, unlike more cohesive tissues, the early embryo dissipates tensile forces required by constricting cells via their neighbors, thereby allowing confined cell repositioning without jeopardizing global architecture.Fil: Samarage, Chaminda R.. Monash University; AustraliaFil: White, Melanie D.. Monash University; AustraliaFil: Alvarez, Yanina Daniela. Monash University; Australia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fierro González, Juan Carlos. Monash University; AustraliaFil: Henon, Yann. Monash University; AustraliaFil: Jesudason, Edwin C.. National Health Service Scotland; Reino UnidoFil: Bissiere, Stephanie. Monash University; Australia. Institute of Molecular and Cell Biology; SingapurFil: Fouras, Andreas. Monash University; AustraliaFil: Plachta, Nicolas. Monash University; Australia. Institute of Molecular and Cell Biology; Singapu

SERCA directs cell migration and branching across species and germ layers

Branching morphogenesis underlies organogenesis in vertebrates and invertebrates, yet is incompletely understood. Here, we show that the sarco-endoplasmic reticulum Ca2+ reuptake pump (SERCA) directs budding across germ layers and species. Clonal knockdown demonstrated a cell-autonomous role for SERCA in Drosophila air sac budding. Live imaging of Drosophila tracheogenesis revealed elevated Ca2+ levels in migratory tip cells as they form branches. SERCA blockade abolished this Ca2+ differential, aborting both cell migration and new branching. Activating protein kinase C (PKC) rescued Ca2+ in tip cells and restored cell migration and branching. Likewise, inhibiting SERCA abolished mammalian epithelial budding, PKC activation rescued budding, while morphogens did not. Mesoderm (zebrafish angiogenesis) and ectoderm (Drosophila nervous system) behaved similarly, suggesting a conserved requirement for cell-autonomous Ca2+ signaling, established by SERCA, in iterative budding

Metagenomic next-generation sequencing aids the diagnosis of viral infections in febrile returning travellers

Objectives Travel-associated infections are challenging to diagnose because of the broad spectrum of potential aetiologies. As a proof-of-principle study, we used MNGS to identify viral pathogens in clinical samples from returning travellers in a single center to explore its suitability as a diagnostic tool. Methods Plasma samples from 40 returning travellers presenting with a fever of ≥38°C were sequenced using MNGS on the Illumina MiSeq platform and compared with standard-of-care diagnostic assays. Results In total, 11/40 patients were diagnosed with a viral infection. Standard of care diagnostics revealed 5 viral infections using plasma samples; dengue virus 1 (n = 2), hepatitis E (n = 1), Ebola virus (n = 1) and hepatitis A (n = 1), all of which were detected by MNGS. Three additional patients with Chikungunya virus (n = 2) and mumps virus were diagnosed by MNGS only. Respiratory infections detected by nasal/throat swabs only were not detected by MNGS of plasma. One patient had infection with malaria and mumps virus during the same admission. Conclusions MNGS analysis of plasma samples improves the sensitivity of diagnosis of viral infections and has potential as an all-in-one diagnostic test. It can be used to identify infections that have not been considered by the treating physician, co-infections and new or emerging pathogens. Summary Next generation sequencing (NGS) has potential as an all-in-one diagnostic test. In this study we used NGS to diagnose returning travellers with acute febrile illness in the UK, highlighting cases where the diagnosis was missed using standard methods

The Symptom Monitoring with Feedback Trial (SWIFT):protocol for a registry‑based cluster randomised controlled trial in haemodialysis

BACKGROUND: Kidney failure prevalence is increasing worldwide. Haemodialysis, peritoneal dialysis or kidney transplantation are undertaken to extend life with kidney failure. People receiving haemodialysis commonly experience fatigue, pain, nausea, cramping, itching, sleeping difficulties, anxiety and depression. This symptom burden contributes to poor health-related quality of life (QOL) and is a major reason for treatment withdrawal and death. The Symptom monitoring WIth Feedback Trial (SWIFT) will test the hypothesis that regular symptom monitoring with feedback to people receiving haemodialysis and their treating clinical team can improve QOL. METHODS: We are conducting an Australia and New Zealand Dialysis and Transplant (ANZDATA) registry-based cluster randomised controlled trial to determine the clinical- and cost-effectiveness at 12 months, of 3-monthly symptom monitoring using the Integrated Palliative Outcome Scale-Renal (IPOS-Renal) survey with clinician feedback, compared with usual care among adults treated with haemodialysis. Participants complete symptom scoring using a tablet, which are provided to participants and to clinicians. The trial aims to recruit 143 satellite haemodialysis centres, (up to 2400 participants). The primary outcome is change in health-related QOL, as measured by EuroQol 5-Dimension, 5-Level (EQ-5D-5L) instrument. Secondary outcomes include overall survival, symptom severity (including haemodialysis-associated fatigue), healthcare utilisation and cost-effectiveness. DISCUSSION: SWIFT is the first registry-based trial in the Australian haemodialysis population to investigate whether regular symptom monitoring with feedback to participants and clinicians improves QOL. SWIFT is embedded in the ANZDATA Registry facilitating pragmatic recruitment from public and private dialysis clinics, throughout Australia. SWIFT will inform future collection, storage and reporting of patient-reported outcome measures (PROMs) within a clinical quality registry. As the first trial to rigorously estimate the efficacy and cost-effectiveness of routine PROMs collection and reporting in haemodialysis units, SWIFT will provide invaluable information to health services, clinicians and researchers working to improve the lives of those with kidney failure. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12620001061921. Registered on 16 October 2020 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06355-0

CMMSE2017: On two classes of fourth- and seventh-order vectorial methods with stable behavior

[EN] A family of fourth-order iterative methods without memory, for solving nonlinear systems, and its seventh-order extension, are analyzed. By using complex dynamics tools, their stability and reliability are studied by means of the properties of the rational function obtained when they are applied on quadratic polynomials. The stability of their fixed points, in terms of the value of the parameter, its critical points and their associated parameter planes, etc. give us important information about which members of the family have good properties of stability and whether in any of them appear chaos in the iterative process. The conclusions obtained in this dynamical analysis are used in the numerical section, where an academical problem and also the chemical problem of predicting the diffusion and reaction in a porous catalyst pellet are solved.This research was partially supported by Ministerio de Economia y Competitividad MTM2014-52016-C02-2-P and Generalitat Valenciana PROMETEO/2016/089.Cordero Barbero, A.; Guasp, L.; Torregrosa Sánchez, JR. (2018). CMMSE2017: On two classes of fourth- and seventh-order vectorial methods with stable behavior. Journal of Mathematical Chemistry. 56(7):1902-1923. https://doi.org/10.1007/s10910-017-0814-0S19021923567S. Amat, S. Busquier, Advances in Iterative Methods for Nonlinear Equations (Springer, Berlin, 2016)S. Amat, S. Busquier, S. Plaza, Review of some iterative root-finding methods from a dynamical point of view. Sci. Ser. A Math. Sci. 10, 3–35 (2004)S. Amat, S. Busquier, S. Plaza, A construction of attracting periodic orbits for some classical third-order iterative methods. Comput. Appl. Math. 189, 22–33 (2006)I.K. Argyros, Á.A. Magreñn, On the convergence of an optimal fourth-order family of methods and its dynamics. Appl. Math. Comput. 252, 336–346 (2015)D.K.R. Babajee, A. Cordero, J.R. Torregrosa, Study of multipoint iterative methods through the Cayley quadratic test. Comput. Appl. Math. 291, 358–369 (2016). doi: 10.1016/J.CAM.2014.09.020P. Blanchard, The dynamics of Newton’s method. Proc. Symp. Appl. Math. 49, 139–154 (1994)F.I. Chicharro, A. Cordero, J.R. Torregrosa, Drawing dynamical and parameters planes of iterative families and methods. Sci. World J. 2013, Article ID 780153 (2013)C. Chun, M.Y. Lee, B. Neta, J. Džunić, On optimal fourth-order iterative methods free from second derivative and their dynamics. Appl. Math. Comput. 218, 6427–6438 (2012)A. Cordero, E. Gómez, J.R. Torregrosa, Efficient high-order iterative methods for solving nonlinear systems and their application on heat conduction problems. Complexity 2017, Article ID 6457532 (2017)A. Cordero, J.R. Torregrosa, Variants of Newton’s method using fifth-order quadrature formulas. Appl. Math. Comput. 190, 686–698 (2007)R.L. Devaney, An Introduction to Chaotic Dynamical Systems (Addison-Wesley Publishing Company, Reading, 1989)P.G. Logrado, J.D.M. Vianna, Partitioning technique procedure revisited: formalism and first application to atomic problems. Math. Chem. 22, 107–116 (1997)C.G. Jesudason, I. Numerical nonlinear analysis: differential methods and optimization applied to chemical reaction rate determination. Math. Chem. 49, 1384–1415 (2011)Á.A. Magreñán, Different anomalies in a Jarratt family of iterative root-finding methods. Appl. Math. Comput. 233, 29–38 (2014)M. Mahalakshmi, G. Hariharan, K. Kannan, The wavelet methods to linear and nonlinear reaction-diffusion model arising in mathematical chemistry. Math. Chem. 51(9), 2361–2385 (2013)K. Maleknejad, M. Alizadeh, An efficient numerical scheme for solving Hammerstein integral equation arisen in chemical phenomenon. Proc. Comput. Sci. 3, 361–364 (2011)B. Neta, C. Chun, M. Scott, Basins of attraction for optimal eighth-order methods to find simple roots of nonlinear equations. Appl. Math. Comput. 227, 567–592 (2014)M.S. Petković, B. Neta, L.D. Petković, J. Džunić, Multipoint Methods for Solving Nonlinear Equations (Elsevier, Amsterdam, 2013)R.C. Rach, J.S. Duan, A.M. Wazwaz, Solving coupled Lane–Emden boundary value problems in catalytic diffusion reactions by the Adomian decomposition method. Math. Chem. 52(1), 255–267 (2014)R. Singh, G. Nelakanti, J. Kumar, A new effcient technique for solving two-point boundary value problems for integro-differential equations. Math. Chem. 52, 2030–2051 (2014

Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol.

Background: This study sought to establish the long-term effects of Covid-19 following hospitalisation. Methods: 327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L). Findings: 55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse following acute illness (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age. Interpretation: Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females. Funding: National Institute for Health Research, UK Medical Research Council, Wellcome Trust, Department for International Development and the Bill and Melinda Gates Foundation