Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide. Discovered 30 years ago, it is produced as a consequence of alternative RNA processing of the calcitonin gene. CGRP has two ...major forms (α and β). It belongs to a group of peptides that all act on an unusual receptor family. These receptors consist of calcitonin receptor-like receptor (CLR) linked to an essential receptor activity modifying protein (RAMP) that is necessary for full functionality. CGRP is a highly potent vasodilator and, partly as a consequence, possesses protective mechanisms that are important for physiological and pathological conditions involving the cardiovascular system and wound healing. CGRP is primarily released from sensory nerves and thus is implicated in pain pathways. The proven ability of CGRP antagonists to alleviate migraine has been of most interest in terms of drug development, and knowledge to date concerning this potential therapeutic area is discussed. Other areas covered, where there is less information known on CGRP, include arthritis, skin conditions, diabetes, and obesity. It is concluded that CGRP is an important peptide in mammalian biology, but it is too early at present to know if new medicines for disease treatment will emerge from our knowledge concerning this molecule.
Rapidly rotating Rayleigh-Bénard convection is studied by combining results from direct numerical simulations (DNS), laboratory experiments, and asymptotic modeling. The asymptotic theory is shown to ...provide a good description of the bulk dynamics at low, but finite Rossby number. However, large deviations from the asymptotically predicted heat transfer scaling are found, with laboratory experiments and DNS consistently yielding much larger Nusselt numbers than expected. These deviations are traced down to dynamically active Ekman boundary layers, which are shown to play an integral part in controlling heat transfer even for Ekman numbers as small as 10^{-7}. By adding an analytical parametrization of the Ekman transport to simulations using stress-free boundary conditions, we demonstrate that the heat transfer jumps from values broadly compatible with the asymptotic theory to states of strongly increased heat transfer, in good quantitative agreement with no-slip DNS and compatible with the experimental data. Finally, similarly to nonrotating convection, we find no single scaling behavior, but instead that multiple well-defined dynamical regimes exist in rapidly rotating convection systems.
Some patients with idiopathic pulmonary fibrosis experience acute exacerbations in their respiratory status leading to substantial morbidity and mortality. Occult aspiration of gastric contents has ...been proposed as one possible mechanism leading to these acute exacerbations. We sought to determine whether pepsin, a marker of gastric aspiration, is elevated in bronchoalveolar lavage fluid obtained from patients during acute exacerbation of idiopathic pulmonary fibrosis, compared with that obtained in stable disease. Lavage samples were obtained in a case-control study of well-characterised patients. Acute exacerbation was defined using standard criteria. Levels of lavage pepsin were compared in cases and controls, and were correlated with clinical features and disease course. 24 cases with acute exacerbations and 30 stable controls were identified. There were no significant differences in baseline demographics between the two groups. Pepsin level was an indicator of acute exacerbation status (p=0.04). On average, pepsin appeared higher in patients with acute exacerbations compared with stable controls. This difference was driven by a subgroup of eight patients (33%) with pepsin levels ≥70 ng·mL(-1). Pepsin level was not an independent predictor of survival time. These results suggest occult aspiration may play a role in some cases of acute exacerbation of idiopathic pulmonary fibrosis.
In order to address this question, we consider a simple renormalizable and gauge invariant model in which the Z′ only has couplings to the electron and muon and their associated neutrinos, arising ...from mixing with a heavy vectorlike fourth family of leptons. Within this model we discuss the contributions to the electron and muon anomalous magnetic moments from Z′ exchange, subject to the constraints from μ → e γ and neutrino trident production. Using analytic and numerical arguments, we find that such a Z′ model can account for either the electron or the muon g − 2 anomalies, but not both, while remaining consistent with the experimental constraints from μ → eγ and neutrino trident production.
Objectives: The luminal surface of the gut is lined with a monolayer of epithelial cells that acts as a nutrient absorptive engine and protective barrier. To maintain its integrity and ...functionality, the epithelium is renewed every few days. Theoretical models are powerful tools that can be used to test hypotheses concerning the regulation of this renewal process, to investigate how its dysfunction can lead to loss of homeostasis and neoplasia, and to identify potential therapeutic interventions. Here we propose a new multiscale model for crypt dynamics that links phenomena occurring at the subcellular, cellular and tissue levels of organisation.
Methods: At the subcellular level, deterministic models characterise molecular networks, such as cell‐cycle control and Wnt signalling. The output of these models determines the behaviour of each epithelial cell in response to intra‐, inter‐ and extracellular cues. The modular nature of the model enables us to easily modify individual assumptions and analyse their effects on the system as a whole.
Results: We perform virtual microdissection and labelling‐index experiments, evaluate the impact of various model extensions, obtain new insight into clonal expansion in the crypt, and compare our predictions with recent mitochondrial DNA mutation data.
Conclusions: We demonstrate that relaxing the assumption that stem‐cell positions are fixed enables clonal expansion and niche succession to occur. We also predict that the presence of extracellular factors near the base of the crypt alone suffices to explain the observed spatial variation in nuclear beta‐catenin levels along the crypt axis.
We confirm the recent prediction that interstitial protium may act as a shallow donor in zinc oxide, by direct spectroscopic observation of its muonium counterpart. On implantation into ZnO, positive ...muons--chemically analogous to protons in this context--form paramagnetic centers below about 40 K. The muon-electron contact hyperfine interaction, as well as the temperature and activation energy for ionization, imply a shallow level. Similar results for the cadmium chalcogenides suggest that such shallow donor states are generic to the II-VI compounds. The donor level depths should serve as a guide for the electrical activity of interstitial hydrogen.
We formally introduce 14 new high-level stratigraphic names to augment existing names and to hierarchically organise all of New Zealand's onland and offshore Cambrian-Holocene rocks and ...unconsolidated deposits. The two highest-level units are Austral Superprovince (new) and Zealandia Megasequence (new). These encompass all stratigraphic units of the country's Cambrian-Early Cretaceous basement rocks and Late Cretaceous-Holocene cover rocks and sediments, respectively. Most high-level constituents of the Austral Superprovince are in current and common usage: Eastern and Western Provinces consist of 12 tectonostratigraphic terranes, 10 igneous suites, 5 batholiths and Haast Schist. Ferrar, Tarpaulin and Jaquiery suites (new) have been added to existing plutonic suites to describe all known compositional variation in the Tuhua Intrusives. Zealandia Megasequence consists of five predominantly sedimentary, partly unconformity-bounded units and one igneous unit. Momotu and Haerenga supergroups (new) comprise lowermost rift to passive margin (terrestrial to marine transgressive) rock units. Waka Supergroup (new) includes rocks related to maximum marine flooding linked to passive margin culmination in the east and onset of new tectonic subsidence in the west. Māui and Pākihi supergroups (new) comprise marine to terrestrial regressive rock and sediment units deposited during Neogene plate convergence. Rūaumoko Volcanic Region (new) is introduced to include all igneous rocks of the Zealandia Megasequence and contains the geochemically differentiated Whakaari, Horomaka and Te Raupua supersuites (new). Our new scheme, Litho2014, provides a complete, high-level stratigraphic classification for the continental crust of the New Zealand region.
Background. Whether community-associated methicillin-resistant Staphylococcus aureus (MRSA) genotypes (e.g., USA300) are a major cause of bloodstream infections (BSIs) and health care—associated ...infections has been poorly defined. Methods. Consecutive MRSA isolates recovered from patients with BSIs were prospectively collected at an urban public hospital. Molecular typing studies were performed. Prevalence and risk factors for the MRSA USA300 genotype were assessed. Results. One hundred thirty-two cases of MRSA BSI were documented over 7.5 months in 2004 (incidence, 6.79 per 1000 admissions); 116 isolates were available for genotyping. Characteristics of the 116 evaluable cases included: a mean age 47 years; 62% were male, 82% were African American, and 22% were HIV seropositive. The crude in-hospital mortality rate was 22%. In 107 cases (92%), there was contact with a health care facility within the year prior to infection, and a nosocomial infection (defined as positive blood culture results obtained >48 h after admission) occurred in 49 cases (42%). PFGE demonstrated that 39 (34%) of the 116 isolates were the MRSA USA300 genotype; 34 (29%) were USA100; 42 (36%) were USA500; and 1 (1%) was USA800. MRSA USA300 accounted for 28% of health care—associated BSIs and 20% of nosocomial MRSA BSIs. In multivariate analysis, isolation of the USA300 genotype was associated with injectiondrug use (OR, 3.67; 95% CI, 1.10–12.28) and skin and soft tissue infection (OR, 4.26; 95% CI, 1.08–16.84). Patients who resided in long-term care facilities (OR, 0.09; 95% CI, 0.01–0.82) and those who were treated with antimicrobials in the prior year were less likely to have MRSA USA300 genotype recovered (OR, 0.10; 95% CI, 0.02–0.49). Conclusions. MRSA USA300 genotype, the predominant cause of community-associated MRSA infections in our area (Atlanta, GA), has now emerged as a significant cause of health care—associated and nosocomial BSI. MRSA USA300 as a nosocomial pathogen presents new challenges to infection control programs.
To cite this article: Cummings AJ, Knibb RC, King RM, Lucas JS. The psychosocial impact of food allergy and food hypersensitivity in children, adolescents and their families: a review. Allergy 2010; ...65: 933-945. Food allergy affects 6% of children but there is no cure, and strict avoidance of index allergens along with immediate access to rescue medication is the current best management. With specialist care, morbidity from food allergy in children is generally low, and mortality is very rare. However, there is strong evidence that food allergy and food hypersensitivity has an impact on psychological distress and on the quality of life (QoL) of children and adolescents, as well as their families. Until recently, the measurement of QoL in allergic children has proved difficult because of the lack of investigative tools available. New instruments for assessing QoL in food allergic children have recently been developed and validated, which should provide further insights into the problems these children encounter and will enable us to measure the effects of interventions in patients. This review examines the published impact of food allergy on affected children, adolescents and their families. It considers influences such as gender, age, disease severity, co-existing allergies and external influences, and examines how these may impact on allergy-related QoL and psychological distress including anxiety and depression. Implications of the impact are considered alongside avenues for future research.
Rapid bifurcations in the plasma response to slowly varying n=2 magnetic fields are observed as the plasma transitions into and out of edge-localized mode (ELM) suppression. The rapid transition to ...ELM suppression is characterized by an increase in the toroidal rotation and a reduction in the electron pressure gradient at the top of the pedestal that reduces the perpendicular electron flow there to near zero. These events occur simultaneously with an increase in the inner-wall magnetic response. These observations are consistent with strong resonant field penetration of n=2 fields at the onset of ELM suppression, based on extended MHD simulations using measured plasma profiles. Spontaneous transitions into (and out of) ELM suppression with a static applied n=2 field indicate competing mechanisms of screening and penetration of resonant fields near threshold conditions. Magnetic measurements reveal evidence for the unlocking and rotation of tearinglike structures as the plasma transitions out of ELM suppression.
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