Do grandparents matter? : The impact of Grandparenting on the wellbeing of children

This timely and important report shows the immense value of grandparents in 21st century family life. It reveals a unique relationship that exists between the older generation and the youngest: a relationship of love and trust that enables the children to use their grandparents as confidantes and counsellors as well as playmates and cookery instructors. The report shows that children value the non-critical support, emotional advice and guidance that grandparents offer and enjoy the quality time their grandparents give them. It also found that the relationship has benefits for grandparents adding to their raison d’être and contributing to their health and longevity. The report also notes the change in the nature of family relationships in Britain throughout the 20th century, from the extended family to the nuclear family to the current variety of relationships, formal and informal, in which both the elderly and the young suffer neglect. With today’s increased incidence of divorce and family breakdown, grandparents can sometimes provide the only stable family relationship in a child’s life, and yet grandparents often lose contact with their grandchildren during or after a divorce or relationship breakup and have no legal rights through the Family Court to continue offering loving care and support to their grandchildren. The report concludes that there is need for much greater understanding of the role and function of grandparents in family life today.Final Published versio

“Esperanza, en suma” de una nueva vida mexicana en Pedro Páramo

A partir de la victoria mexicana en la Guerra de Independencia contra España que terminó en 1821, los campesinos de la nación tuvieron que empezar una lucha nueva contra el sistema de caudillos elitistas. A pesar de muchas revoluciones, la destrucción del caudillismo afligió a México por décadas. En Pedro Páramo (1955), Juan Rulfo creó una novela, influida por experiencias personales que también muestra los efectos de la Revolución Mexicana y propone la esperanza de una edad nueva, sin la opresión de los caudillos. Porque tanto la vida de Rulfo como la historia de México tienen un papel muy importante en sus escritos, este trabajo examina ambas, siguiendo con una evaluación de Pedro Páramo como un retrato histórico de la sociedad mexicana durante y después de la Revolución. Se aprecia así que con esta novela, Rulfo produjo una obra pionera de vanguardia que, al incorporar y recrear eventos biográficos e históricos, sugiere vital la “esperanza, en suma” de ese México revolucionario

A new integrated care pathway for ambulance attended severe hypoglycaemia in the East of England: The Eastern Academic Health Science Network (EAHSN) model

Aims: We developed a new clinical integrated pathway linking a regional Ambulance Trust with a severe hypoglycaemia (SH) prevention team. We present clinical data from the first 2,000 emergency calls taken through this new clinical pathway in the East of England. Methods: SH patients attended by Ambulance crew receive written information on SH avoidance, and are contacted for further education through a new regional SH prevention team. All patients are contacted unless they actively decline. Results: Median age (IQR) was 67 (50 - 80) years, 23.6% of calls were for patients over 80 years old, and patients more than 90 years old were more common than 20 - 25 year olds in this population. Most calls were for patients (84.9%) who were insulin treated, even those over 80 years (75%). One - third of patients attended after a call were unconscious on attendance. 5.6% of patients in this call population had 3 or more ambulance call outs, and they generated 17.6% of all calls. In total, 728 episodes (36.4%) were repeat calls. Insulin related events were clinically more severe than oral hypoglycaemic related events. Patients conveyed to hospitals (13.8%) were significantly older, with poorer recovery in biochemical hypoglycaemia after ambulance crew attendance. Only 19 (1%) opted out of further contact. Patients were contacted by the SH prevention team after a median 3 (0 - 6) days. The most common patient self - reported cause for their SH episode was related to percieved errors in insulin management (31.4%). Conclusions: This new clinical service is simple, acceptable to patients, and a translatable model for prevention of recurrent SH in this largely elderly insulin treated SH population

The Stereotypic Response of the Pulmonary Vasculature to Respiratory Viral Infections: Findings in Mouse Models of SARS-CoV-2, Influenza A and Gammaherpesvirus Infections

The respiratory system is the main target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 19 (COVID-19) where acute respiratory distress syndrome is considered the leading cause of death. Changes in pulmonary blood vessels, among which an endothelialitis/endotheliitis has been particularly emphasized, have been suggested to play a central role in the development of acute lung injury. Similar vascular changes are also observed in animal models of COVID-19. The present study aimed to determine whether the latter are specific for SARS-CoV-2 infection, investigating the vascular response in the lungs of mice infected with SARS-CoV-2 and other respiratory viruses (influenza A and murine gammaherpesvirus) by in situ approaches (histology, immunohistology, morphometry) combined with RNA sequencing and bioinformatic analysis. Non-selective recruitment of monocytes and T and B cells from larger muscular veins and arteries was observed with all viruses, matched by a comparable transcriptional response. There was no evidence of endothelial cell infection in any of the models. Both the morphological investigation and the transcriptomics approach support the interpretation that the lung vasculature in mice mounts a stereotypic response to alveolar and respiratory epithelial damage. This may have implications for the treatment and management of respiratory disease in humans

The discovery of potent, selective, and reversible inhibitors of the house dust mite peptidase allergen Der p 1: an innovative approach to the treatment of allergic asthma.

Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma

Tissue proteomic analysis identifies mechanisms and stages of immunopathology in fatal COVID-19

Funding: This work was funded by UK Research and Innovation (UKRI) (Coronavirus Disease [COVID-19] Rapid Response Initiative; MR/V028790/1 to C.D.L., D.A.D., and J.A.H.), LifeArc (through the University of Edinburgh STOPCOVID funding award, to K.D, D.A.D., C.D.L), The Chief Scientist Office (RARC-19 Funding Call, ‘Inflammation in Covid-19: Exploration of Critical Aspects of Pathogenesis; COV/EDI/20/10’ to D.A.D, C.D.L, C.D.R, J.K.B and D.J.H), and Medical Research Scotland (CVG-1722- 2020 to DAD, CDL, CDR, JKB, and DJH). C.D.L is funded by a Wellcome Trust Clinical Career Development Fellowship (206566/Z/17/Z). J.K.B. and C.D.R. are supported by the Medical Research Council (grant MC_PC_19059) as part of the ISARIC Coronavirus Clinical Characterisation Consortium (ISARIC-4C). C.D.R. is supported by an Edinburgh Clinical Academic Track (ECAT)/Wellcome Trust PhD Training Fellowship for Clinicians award (214178/Z/18/Z). J.A.H. is supported by the U.S. Food and Drug Administration (contract 75F40120C00085, Characterization of severe coronavirus infection in humans and model systems for medical countermeasure development and evaluation’). G.C.O is funded by an NRS Clinician award. N.N.G. is funded by a Pathological Society Award. A.R.A. is supported by a Cancer Research UK Clinician Scientist Fellowship award (A24867).Immunopathology occurs in the lung and spleen in fatal COVID-19, involving monocytes/macrophages and plasma cells. Anti-inflammatory therapy reduces mortality but additional therapeutic targets are required. We aimed to gain mechanistic insight into COVID-19 immunopathology by targeted proteomic analysis of pulmonary and splenic tissues. Lung parenchymal and splenic tissue was obtained from 13 post-mortem examinations of patients with fatal COVID-19. Control tissue was obtained from cancer resection samples (lung) and deceased organ donors (spleen). Protein was extracted from tissue by phenol extraction. Olink® multiplex immunoassay panels were used for protein detection and quantification. Proteins with increased abundance in the lung included MCP-3, antiviral TRIM21 and pro-thrombotic TYMP. OSM and EN-RAGE/S100A12 abundance was correlated, and associated with inflammation severity. Unsupervised clustering identified ‘early viral’ and ‘late inflammatory’ clusters with distinct protein abundance profiles, and differences in illness duration prior to death and presence of viral RNA. In the spleen, lymphocyte chemotactic factors and CD8A were decreased in abundance, and pro-apoptotic factors were increased. B-cell receptor signalling pathway components and macrophage colony stimulating factor (CSF-1) were also increased. Additional evidence for a sub-set of host factors (including DDX58, OSM, TYMP, IL-18, MCP-3 and CSF-1) was provided by overlap between (i) differential abundance in spleen and lung tissue, (ii) meta-analysis of existing datasets, and (iii) plasma proteomic data. This proteomic analysis of lung parenchymal and splenic tissue from fatal COVID-19 provides mechanistic insight into tissue anti-viral responses, inflammation and disease stages, macrophage involvement, pulmonary thrombosis, splenic B-cell activation and lymphocyte depletion.Publisher PDFPeer reviewe

TU Tau B: The Peculiar 'Eclipse' of a possible proto-Barium Giant

TU Tau (= HD 38218 = HIP 27135) is a binary system consisting of a C-N carbon star primary and an A-type secondary. We report on new photometry and spectroscopy which tracked the recent disappearance of the A-star secondary. The dimming of the A-star was gradual and irregular, with one or more brief brightenings, implying the presence of nonhomogeneities in the carbon star outflow. We also present evidence that the A-star is actively accreting s-process enriched material from the carbon star and suggest that it will therefore eventually evolve into a Barium giant. This is an important system as well because the A-type star can serve as a probe of the outer atmosphere of the carbon star.Comment: 9 pages, 9 figures, 4 tables, a number of amateur observatories made significant contributions to this research. Paper accepted for publication in The Astronomical Journa

Endophytic bacterial community composition in wheat (Triticum aestivum) is determined by plant tissue type, developmental stage and soil nutrient availability

Aims: To understand effects of tissue type, growth stage and soil fertilisers on bacterial endophyte communities of winter wheat (Triticum aestivum cv. Hereward). Methods: Endophytes were isolated from wheat grown under six fertiliser conditions in the long term Broadbalk Experiment at Rothamsted Research, UK. Samples were taken in May and July from root and leaf tissues. Results: Root and leaf communities differed in abundance and composition of endophytes. Endophytes were most abundant in roots and the Proteobacteria were most prevalent. In contrast, Firmicutes and Actinobacteria, the Gram positive phyla, were most prevalent in the leaves. Both fertiliser treatment and sample time influenced abundance and relative proportions of each phylum and genus in the endosphere. A higher density of endophytes was found in the Nil input treatment plants. Conclusions: Robust isolation techniques and stringent controls are critical for accurate recovery of endophytes. The plant tissue type, plant growth stage, and soil fertiliser treatment all contribute to the composition of the endophytic bacterial community in wheat. These results should help facilitate targeted development of endophytes for beneficial applications in agriculture