643 research outputs found
Family centred neonatal palliative care in children's hospices: A qualitative study of parents' experiences
Since 1982, children's hospices in the UK have provided services where families can care for their children at the end of life (EOL) in a less medicalised environment. More recently, the services of many children's hospices have extended to newborn babies and their families. This paper explores the experiences of three families (five parents) who availed of children's hospices services when their babies required a palliative approach to care. Early diagnosis of a life-limiting condition in pregnancy allowed advanced care planning and enabled parental participation in decision-making before birth. A homely environment, as well as constant support and a sensitive approach from expert staff encouraged parental involvement in all aspects of their baby's care whilst in hospice. Extended time with their baby after death enabled parents to feel connected with their infant. The holistic and family-centred approach to care from children's hospices is highly valued by parents of newborn babies
Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth
Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations
A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci
The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function
Composite Higgs Search at the LHC
The Higgs boson production cross-sections and decay rates depend, within the
Standard Model (SM), on a single unknown parameter, the Higgs mass. In
composite Higgs models where the Higgs boson emerges as a pseudo-Goldstone
boson from a strongly-interacting sector, additional parameters control the
Higgs properties which then deviate from the SM ones. These deviations modify
the LEP and Tevatron exclusion bounds and significantly affect the searches for
the Higgs boson at the LHC. In some cases, all the Higgs couplings are reduced,
which results in deterioration of the Higgs searches but the deviations of the
Higgs couplings can also allow for an enhancement of the gluon-fusion
production channel, leading to higher statistical significances. The search in
the H to gamma gamma channel can also be substantially improved due to an
enhancement of the branching fraction for the decay of the Higgs boson into a
pair of photons.Comment: 32 pages, 16 figure
Extragalactic Results from the Infrared Space Observatory
More than a decade ago the IRAS satellite opened the realm of external
galaxies for studies in the 10 to 100 micron band and discovered emission from
tens of thousands of normal and active galaxies. With the 1995-1998 mission of
the Infrared Space Observatory the next major steps in extragalactic infrared
astronomy became possible: detailed imaging, spectroscopy and
spectro-photometry of many galaxies detected by IRAS, as well as deep surveys
in the mid- and far- IR. The spectroscopic data reveal a wealth of detail about
the nature of the energy source(s) and about the physical conditions in
galaxies. ISO's surveys for the first time explore the infrared emission of
distant, high-redshift galaxies. ISO's main theme in extragalactic astronomy is
the role of star formation in the activity and evolution of galaxies.Comment: 106 pages, including 17 figures. Ann.Rev.Astron.Astrophys. (in
press), a gzip'd pdf file (667kB) is also available at
http://www.mpe.mpg.de/www_ir/preprint/annrev2000.pdf.g
Persistence within dendritic cells marks an antifungal evasion and dissemination strategy of Aspergillus terreus
Aspergillus terreus is an airborne human fungal pathogen causing life-threatening invasive aspergillosis in immunocompromised patients. In contrast to Aspergillus fumigatus, A. terreus infections are associated with high dissemination rates and poor response to antifungal treatment. Here, we compared the interaction of conidia from both fungal species with MUTZ-3-derived dendritic cells (DCs). After phagocytosis, A. fumigatus conidia rapidly escaped from DCs, whereas A. terreus conidia remained persisting with long-term survival. Escape from DCs was independent from DHN-melanin, as A. terreus conidia expressing wA showed no increased intracellular germination. Within DCs A. terreus conidia were protected from antifungals, whereas A. fumigatus conidia were efficiently cleared. Furthermore, while A. fumigatus conidia triggered expression of DC activation markers such as CD80, CD83, CD54, MHCII and CCR7, persistent A. terreus conidia were significantly less immunogenic. Moreover, DCs confronted with A. terreus conidia neither produced pro-inflammatory nor T-cell stimulating cytokines. However, TNF-α addition resulted in activation of DCs and provoked the expression of migration markers without inactivating intracellular A. terreus conidia. Therefore, persistence within DCs and possibly within other immune cells might contribute to the low response of A. terreus infections to antifungal treatment and could be responsible for its high dissemination rates
Linguistic and maternal genetic diversity are not correlated in Native Mexicans
Mesoamerica, defined as the broad linguistic and cultural area from middle southern Mexico to Costa Rica, might have played a pivotal role during the colonization of the American continent. The Mesoamerican isthmus has constituted an important geographic barrier that has severely restricted gene flow between North and South America in pre-historical times. Although the Native American component has been already described in admixed Mexican populations, few studies have been carried out in native Mexican populations. In this study, we present mitochondrial DNA (mtDNA) sequence data for the first hypervariable region (HVR-I) in 477 unrelated individuals belonging to 11 different native populations from Mexico. Almost all of the Native Mexican mtDNAs could be classified into the four pan-Amerindian haplogroups (A2, B2, C1, and D1); only two of them could be allocated to the rare Native American lineage D4h3. Their haplogroup phylogenies are clearly star-like, as expected from relatively young populations that have experienced diverse episodes of genetic drift (e.g., extensive isolation, genetic drift, and founder effects) and posterior population expansions. In agreement with this observation, Native Mexican populations show a high degree of heterogeneity in their patterns of haplogroup frequencies. Haplogroup X2a was absent in our samples, supporting previous observations where this clade was only detected in the American northernmost areas. The search for identical sequences in the American continent shows that, although Native Mexican populations seem to show a closer relationship to North American populations, they cannot be related to a single geographical region within the continent. Finally, we did not find significant population structure in the maternal lineages when considering the four main and distinct linguistic groups represented in our Mexican samples (Oto-Manguean, Uto-Aztecan, Tarascan, and Mayan), suggesting that genetic divergence predates linguistic diversification in Mexico
Rheological properties of magnetic biogels
We report an experimental and theoretical study of the rheological properties of magnetic biogels
consisting of fibrin polymer networks with embedded magnetite nanoparticles, swollen by aqueous solutions.
We studied two types of magnetic biogels, differenced by the presence or absence of an applied magnetic field
during the initial steps of cross-linking. The experiments demonstrated very strong dependence of the elastic
modulus of the magnetic biogels on the concentration of the magnetic particles. We finally developed some
theoretical models that explain the observed strong concentration effects.This study was supported by projects FIS2013-41821-R (Plan Nacional de Investigación Científica, Desarrollo
e Innovación Tecnológica, MINECO, Spain, co-funded by ERDF, European Union) and FIS2017-85954-R (Ministerio de
Economía, Industria y Competitividad, MINECO, andAgencia Estatal de Investigación, AEI, Spain, co-funded by Fondo Europeo
de Desarrollo Regional, FEDER, European Union). A.Z. is grateful to the program of the Ministry of Education and Science of
the Russian Federation, projects 02.A03.21.0006, 3.1438.2017/4.6, and 3.5214.2017/6.7, as well as to the Russian Fund of Basic
Researches, project 18-08-00178
Detection of Prion Infectivity in Fat Tissues of Scrapie-Infected Mice
Distribution of prion infectivity in organs and tissues is important in understanding prion disease pathogenesis and designing strategies to prevent prion infection in animals and humans. Transmission of prion disease from cattle to humans resulted in banning human consumption of ruminant nervous system and certain other tissues. In the present study, we surveyed tissue distribution of prion infectivity in mice with prion disease. We show for the first time detection of infectivity in white and brown fat. Since high amounts of ruminant fat are consumed by humans and also incorporated into animal feed, fat-containing tissues may pose a previously unappreciated hazard for spread of prion infection
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