RESUMO
Forest edges influence more than half of the world's forests and contribute to worldwide declines in biodiversity and ecosystem functions. However, predicting these declines is challenging in heterogeneous fragmented landscapes. Here we assembled a global dataset on species responses to fragmentation and developed a statistical approach for quantifying edge impacts in heterogeneous landscapes to quantify edge-determined changes in abundance of 1,673 vertebrate species. We show that the abundances of 85% of species are affected, either positively or negatively, by forest edges. Species that live in the centre of the forest (forest core), that were more likely to be listed as threatened by the International Union for Conservation of Nature (IUCN), reached peak abundances only at sites farther than 200-400 m from sharp high-contrast forest edges. Smaller-bodied amphibians, larger reptiles and medium-sized non-volant mammals experienced a larger reduction in suitable habitat than other forest-core species. Our results highlight the pervasive ability of forest edges to restructure ecological communities on a global scale.
Assuntos
Biodiversidade , Florestas , Anfíbios/anatomia & histologia , Animais , Aves/anatomia & histologia , Tamanho Corporal , Mapeamento Geográfico , Mamíferos/anatomia & histologia , Dinâmica Populacional , Répteis/anatomia & histologiaRESUMO
Are the results of randomised trials reliable and are p values and confidence intervals the best way of quantifying efficacy? Low power is common in medical research, which reduces the probability of obtaining a 'significant result' and declaring the intervention had an effect. Metrics derived from Bayesian methods may provide an insight into trial data unavailable from p values and confidence intervals. We did a structured review of multicentre trials in anaesthesia that were published in the New England Journal of Medicine, The Lancet, Journal of the American Medical Association, British Journal of Anaesthesia and Anesthesiology between February 2011 and November 2021. We documented whether trials declared a non-zero effect by an intervention on the primary outcome. We documented the expected and observed effect sizes. We calculated a Bayes factor from the published trial data indicating the probability of the data under the null hypothesis of zero effect relative to the alternative hypothesis of a non-zero effect. We used the Bayes factor to calculate the post-test probability of zero effect for the intervention (having assumed 50% belief in zero effect before the trial). We contacted all authors to estimate the costs of running the trials. The median (IQR [range]) hypothesised and observed absolute effect sizes were 7% (3-13% [0-25%]) vs. 2% (1-7% [0-24%]), respectively. Non-zero effects were declared for 12/56 outcomes (21%). The Bayes factor favouring a zero effect relative to a non-zero effect for these 12 trials was 0.000001-1.9, with post-test zero effect probabilities for the intervention of 0.0001-65%. The other 44 trials did not declare non-zero effects, with Bayes factors favouring zero effect of 1-688, and post-test probabilities of zero effect of 53-99%. The median (IQR [range]) study costs reported by 20 corresponding authors in US$ were $1,425,669 ($514,766-$2,526,807 [$120,758-$24,763,921]). We think that inadequate power and mortality as an outcome are why few trials declared non-zero effects. Bayes factors and post-test probabilities provide a useful insight into trial results, particularly when p values approximate the significance threshold.
Assuntos
Anestesia , Estados Unidos , Humanos , Teorema de BayesRESUMO
The efficiency of intervention for children with speech sound disorder may be influenced by linguistic complexity of the phonological intervention target. Complex targets, particularly, later-acquired, less-known consonants and consonant clusters, have been linked to greater post-intervention generalization to untargeted phonological structures. Yet there is little direct evidence to support target selection based on linguistic complexity for Spanish-speaking children with speech sound disorder. This intervention study utilizes an experimental single-case design to examine the efficacy of intervention in Spanish using different complex targets (i.e. /ɡɾ/, /bɾ/, and /l/). For each of the four Spanish-speaking children with speech sound disorder, sounds at 0% accuracy during baseline were monitored across the baseline period, during and post-intervention, and at one- and two-month follow-up visits. Over the course of intervention, only one participant achieved mastery of the targeted structure in practiced words. However, all participants demonstrated some amount of broad phonological generalization to untargeted consonants or clusters. Variable learning trajectories and broad phonological generalization are discussed as they relate to participant characteristics and linguistic complexity.
Assuntos
Apraxias , Transtornos do Desenvolvimento da Linguagem , Transtorno Fonológico , Gagueira , Criança , Linguagem Infantil , Humanos , Idioma , Fonética , Medida da Produção da Fala , Transtorno Fonológico/terapiaRESUMO
BACKGROUND/OBJECTIVES: Diagnosis of pancreatic cancer is often delayed, contributing to patient and family distress and leading to worse survival. We aimed to develop a decision support tool to support primary care providers to identify patients that should undergo investigations for pancreatic cancer, and to recommend initial diagnostic pathways. METHODS: A modified Delphi process, including a series of three surveys, was undertaken to ascertain clinical expert opinion on which combinations of signs, symptoms and risk factors should be included in a tool for the early identification of pancreatic cancer. A group of clinical specialists finalised the development of the tool during a focus group meeting. RESULTS: The tool presents individual or combinations of signs, symptoms, and risk factors in three tiers which direct the urgency of investigation. Tier 1 includes 5 clinical presentation and risk factors clusters that indicate the need for urgent investigation of the pancreas. A further five clusters are included as Tier 2 aiming to elimate other causes and reduce the time to investigating the pancreas. Tier 3 includes a list of non-specific signs, symptoms and risk factors that indicate the need to consider pancreatic cancer as a potential diagnosis, but without specific recommendations for investigation. CONCLUSIONS: Prospective validation studies are now required prior to implementation in the primary care setting. Implementation into primary care practice and as an educational resource may facilitate rapid diagnosis and improve outcomes such as distress and survival.
Assuntos
Medicina Geral , Neoplasias Pancreáticas , Consenso , Técnica Delphi , Humanos , Neoplasias Pancreáticas/diagnóstico , Inquéritos e QuestionáriosRESUMO
We report on the measurement of the γpâJ/ψp cross section from E_{γ}=11.8 GeV down to the threshold at 8.2 GeV using a tagged photon beam with the GlueX experiment. We find that the total cross section falls toward the threshold less steeply than expected from two-gluon exchange models. The differential cross section dσ/dt has an exponential slope of 1.67±0.39 GeV^{-2} at 10.7 GeV average energy. The LHCb pentaquark candidates P_{c}^{+} can be produced in the s channel of this reaction. We see no evidence for them and set model-dependent upper limits on their branching fractions B(P_{c}^{+}âJ/ψp) and cross sections σ(γpâP_{c}^{+})×B(P_{c}^{+}âJ/ψp).
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Barium esophagrams are a frequently performed test, and radiological observations about potential abnormal esophageal motility, such as tertiary contractions, are commonly reported. We sought to assess the correlation between tertiary waves, and in particular isolated tertiary waves, on esophagrams and findings on non-synchronous high-resolution esophageal manometry. We retrospectively reviewed reports of esophagrams performed at a tertiary referral center and identified patients in whom tertiary waves were observed and a high-resolution esophageal manometry had been performed. We defined two groups; group 1 was defined as patients with isolated tertiary waves, whereas group 2 had tertiary waves and evidence of achalasia or an obstructing structural abnormality on the esophagram. We collected data on demographics, dysphagia score, associated findings on esophagram, and need for intervention. We reviewed the reports of 2100 esophagrams of which tertiary waves were noted as an isolated abnormality in 92, and in association with achalasia or a structural obstruction in 61. High-resolution manometry was performed in 17 patients in group 1, and five had evidence of a significant esophageal motility disorder and 4 required any intervention. Twenty-one patients in group 2 underwent manometry, and 18 had a significant esophageal motility disorder. An isolated finding of tertiary waves on an esophagram is rarely associated with a significant esophageal motility disorder that requires intervention. All patients with isolated tertiary waves who required intervention had a dysphagia to liquids. Tertiary contractions, in the absence of dysphagia to liquids, indicate no significant esophageal motility disorder.
Assuntos
Transtornos da Motilidade Esofágica , Esôfago , Adulto , Idoso , Sulfato de Bário/farmacologia , Meios de Contraste/farmacologia , Transtornos de Deglutição/diagnóstico por imagem , Transtornos de Deglutição/fisiopatologia , Transtornos da Motilidade Esofágica/diagnóstico , Transtornos da Motilidade Esofágica/fisiopatologia , Esôfago/diagnóstico por imagem , Esôfago/fisiopatologia , Feminino , Humanos , Masculino , Manometria/métodos , Pessoa de Meia-Idade , Peristaltismo/fisiologia , Radiografia , Estudos Retrospectivos , Estatística como AssuntoRESUMO
Staphylococcus aureus is a common cause of chronic mammary gland infections in dairy cattle. However, the inflammatory response and duration of infection following pathogen exposure is variable between individual animals. To investigate interanimal differences in immune response, dermal fibroblast cultures were established from skin biopsies collected from 50 early lactation Holstein cows. The fibroblasts ability to produce IL-8 in response to a 24-h treatment with a synthetic toll-like receptor 2/6 agonist (Pam2CSK4) was used to assign a response phenotype to the animals. Five high-responding and 5 low-responding animals were then selected for an intramammary challenge with S. aureus to evaluate differences in the inflammatory response, chronicity of infection, and development of antibodies to the pathogen. All animals exhibited clinical symptoms of mastitis at 24h postchallenge. Animals previously classified as high responders experienced a greater inflammatory response characterized by elevated levels of milk somatic cell count, IL-8, and BSA following the challenge compared with low responders. In addition, antibodies toward the challenge strain of S. aureus reached higher levels in whey from the challenged gland of high responders compared with low responders. Despite the antibody response, all 5 high responders were chronically infected for the 6-wk duration of the study, whereas 2 of the low responders cleared the infection, although 1 of these did become reinfected. The observed differences between animals classified as low and high responders based on their fibroblast responsiveness suggests that this cell type can be used to further examine the causes of interanimal variation in response to mammary infection.
Assuntos
Doenças dos Bovinos/imunologia , Mastite Bovina/imunologia , Infecções Estafilocócicas/veterinária , Staphylococcus aureus/fisiologia , Animais , Bovinos , Doenças dos Bovinos/microbiologia , Contagem de Células/veterinária , Feminino , Fibroblastos/imunologia , Fibroblastos/microbiologia , Interleucina-8/imunologia , Mastite Bovina/microbiologia , Leite/química , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Receptor 2 Toll-Like/agonistas , Receptor 6 Toll-Like/agonistasRESUMO
Marine spatial planning provides a comprehensive framework for managing multiple uses of the marine environment and has the potential to minimize environmental impacts and reduce conflicts among users. Spatially explicit assessments of the risks to key marine species from human activities are a requirement of marine spatial planning. We assessed the risk of ships striking humpback (Megaptera novaeangliae), blue (Balaenoptera musculus), and fin (Balaenoptera physalus) whales in alternative shipping routes derived from patterns of shipping traffic off Southern California (U.S.A.). Specifically, we developed whale-habitat models and assumed ship-strike risk for the alternative shipping routes was proportional to the number of whales predicted by the models to occur within each route. This definition of risk assumes all ships travel within a single route. We also calculated risk assuming ships travel via multiple routes. We estimated the potential for conflict between shipping and other uses (military training and fishing) due to overlap with the routes. We also estimated the overlap between shipping routes and protected areas. The route with the lowest risk for humpback whales had the highest risk for fin whales and vice versa. Risk to both species may be ameliorated by creating a new route south of the northern Channel Islands and spreading traffic between this new route and the existing route in the Santa Barbara Channel. Creating a longer route may reduce the overlap between shipping and other uses by concentrating shipping traffic. Blue whales are distributed more evenly across our study area than humpback and fin whales; thus, risk could not be ameliorated by concentrating shipping traffic in any of the routes we considered. Reducing ship-strike risk for blue whales may be necessary because our estimate of the potential number of strikes suggests that they are likely to exceed allowable levels of anthropogenic impacts established under U.S. laws.
Assuntos
Distribuição Animal , Balaenoptera/fisiologia , Conservação dos Recursos Naturais , Baleia Comum/fisiologia , Jubarte/fisiologia , Animais , California , Ecossistema , Modelos Biológicos , Oceano Pacífico , Dinâmica Populacional , Medição de Risco , Estações do Ano , Navios , Fatores de TempoRESUMO
BACKGROUND: A range of voluntary sector organizations are involved in the delivery of services to children, particularly within the Early Year's sector and children's centres. Peers Early Education Partnership (PEEP) Early Explorers project is one example of the way in which explicit partnerships are being forged across statutory and voluntary sectors with the aim of improving outcomes for children and families. This paper reports an exploration of stakeholder views and experiences of two Early Explorer clinics located in areas of high deprivation. METHODS: Semi-structured interviews were conducted with a purposive sample of stakeholders (n= 25) from children's centres, PEEP, the health visiting service and service users. Data were fully transcribed and analysed using a thematic approach. RESULTS: The data suggest that the two key groups of stakeholders providing Early Explorer clinics (i.e. health visitors and PEEP practitioners) had quite different objectives in terms of their early goals for the clinic, but that despite these differences good progress was achieved in terms of working together effectively. All stakeholders including service users referred to the presence of PEEP as having improved the quality of the clinic environment, and participating mothers identified a wide range of benefits from the enhanced service. However, somewhat restricted views about the role of practitioners within the clinics were identified by users, and the findings suggest that although the early goals for the clinic had been exceeded, these may have been limited in terms of true 'partnership' working. CONCLUSIONS: Early Explorer clinics appeared to have enhanced the service provided within traditional child health clinics and to have provided practitioners with access to hard-to-reach families and parents with access to services that are consistent with the broader policy aims of improving parent-infant interaction. However, questions remain as to whether the benefit of 'partnership' working was fully realized.
Assuntos
Serviços de Saúde da Criança/organização & administração , Enfermagem em Saúde Comunitária/organização & administração , Intervenção Educacional Precoce/organização & administração , Instituições Filantrópicas de Saúde/organização & administração , Atitude do Pessoal de Saúde , Pré-Escolar , Centros Comunitários de Saúde/organização & administração , Relações Comunidade-Instituição , Deficiências do Desenvolvimento/prevenção & controle , Inglaterra , Humanos , Lactente , Áreas de PobrezaRESUMO
BACKGROUND: Many patients attribute their symptoms of facial pain or headache to sinus problems. Facial pain is one of the symptoms of rhinosinusitis according to European and American consensus documents. This symptom, however, has been insufficiently studied in the group of patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The aim of this work is to study the symptom of facial pain in patients with CRSwNP. METHODS: Patients with CRSwNP were prospectively asked to score their facial pain according to the scoring system used in the Sino Nasal Outcome Test 22 (SNOT 22). RESULTS: Fifty patients fulfilled the inclusion criteria. Thirty-one patients had grade II polyps and 19 patients had grade III polyps. Of these patients, 76% had absent or very mild facial pain. Only 16% of patients had moderate or severe facial pain. All patients with severe facial pain had viscid secretions within their sinuses. CONCLUSION: Significant facial pain is uncommon in patients with CRSwNP. It is important to consider this when counselling patients before surgery.
Assuntos
Dor Facial/etiologia , Pólipos Nasais/complicações , Rinite/complicações , Sinusite/complicações , Adolescente , Adulto , Idoso , Distribuição de Qui-Quadrado , Doença Crônica , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos ProspectivosRESUMO
The objective was to evaluate the nutrient intake and digestibility and milk production response of lactating dairy cows fed diets based on corn silage produced from 3 different types of corn hybrids. Experimental diets contained 36.4% of the dietary dry matter (DM) from corn silage produced from normal (Agratech 1021, AgraTech Seeds Inc., Atlanta, GA), brown midrib (BMR; Mycogen F2F797, Mycogen Seeds, Indianapolis, IN), or waxy (Master's Choice 590, Master's Choice Hybrids, Ullin, IL) hybrids. Thirty-six multiparous and primiparous Holstein cows (66 ± 22 d in milk, 41 ± 8 kg/d of milk) were used in an 11-wk completely randomized design trial during the fall of 2009. All cows were fed a diet containing normal corn silage during the first 2wk of the trial before being assigned to 1 of 3 treatments for the following 9 wk. Data collected during the first 2 wk were used as a covariate in the statistical analysis. No difference was observed in dry matter intake (DMI) among treatments, which averaged 22.6 kg/d. Milk yield was higher for cows fed BMR (37.6 kg/d) compared with waxy (35.2 kg/d) but was similar to that of cows fed control (36.2 kg/d). Milk fat percentage tended to be lower for cows fed control (3.28%) compared with those fed BMR (3.60%) or waxy (3.55%) corn silage. Milk protein percentage tended to be lower for cows fed control (2.79%) compared with waxy (2.89%) but similar to that of those fed BMR (2.85%). No differences were observed in yield of milk components. Energy-corrected milk (ECM) yield and dairy efficiency (ECM:DMI) did not differ among treatments. Cows fed BMR tended to gain more body weight compared with those fed control and waxy. Results of this trial are consistent with previous reports in which cows fed diets based on corn silage produced from BMR hybrids have higher milk yield compared with those fed other hybrids. Corn silage produced from the waxy hybrid supported a similar yield of ECM because of higher milk components, but milk yield was not improved compared with the control.
Assuntos
Bovinos/metabolismo , Leite/metabolismo , Silagem , Zea mays , Fenômenos Fisiológicos da Nutrição Animal , Animais , Peso Corporal/fisiologia , Quimera , Ingestão de Alimentos/fisiologia , Fezes/química , Feminino , Lactação , Distribuição AleatóriaRESUMO
A field trial was conducted on 2 US dairy herds to evaluate the transmission dynamics of coagulase-negative staphylococci (CNS) during the lactation period. Quarter milk cultures positive for CNS were classified as intramammary infection (IMI) or incidental isolation (transient colonization). The average proportion of quarters with CNS IMI was 0.114 in farm 1 and 0.09 in farm 2, and corresponding estimates for quarters with transient colonization of CNS were 0.122 and 0.088 throughout the 13-mo study period. Transmission parameters were obtained both for IMI caused by CNS and for CNS-positive quarters classified as the combination of transient colonization and IMI. Transmission between cows and between quarters in the same cow was assessed. The transmission parameters (ß) for IMI caused by CNS were 0.0066 (farm 1) and 0.0111 (farm 2). Corresponding estimates of ß when IMI and transient colonization of CNS were assessed jointly were 0.0256 (farm 1) and 0.0253 (farm 2). On farm 1, risk of transmission for CNS IMI between quarters in the same cow was 2 times greater than that between quarters from cow to cow. Transmission of CNS was considered contagious in one farm but no distinction between contagious and environmental transmission could be made in the other. We hypothesize that between-farm variation may be related to diversity between prevailing CNS species or by differences in management. In the current study, estimates of the basic reproduction number (R(0)) at the farm level for CNS IMI were 0.59 and 0.84 in farms 1 and 2, respectively. This shows that the transmission of CNS from IMI during the lactation period would to be too low to maintain the observed herd prevalence of CNS IMI. The R(0) values for the combination of transient colonization and IMI by CNS were 1.13 and 1.17 in farms 1 and 2, respectively. This indicates potential for sustained endemic infection of CNS throughout lactation. However, prevailing CNS species may also differ between transient colonization and IMI. Therefore, not only CNS originating from IMI or incidental isolation events, but also CNS IMI occurring from the period outside the lactation pen are essential for maintenance of the observed herd prevalence of CNS IMI throughout lactation in this study. The effect of IMI originating outside the lactation pen was verified in simulations with reduced entry of infectious quarters to the lactation pens. Measures against CNS IMI would probably increase in efficiency if prevention of infection during the dry period and early lactation were further emphasized in herd health programs.
Assuntos
Mastite Bovina/transmissão , Infecções Estafilocócicas/veterinária , Staphylococcus/metabolismo , Animais , Bovinos , Feminino , Lactação , Glândulas Mamárias Animais/microbiologia , Mastite Bovina/microbiologia , Leite/microbiologia , Modelos Estatísticos , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/transmissãoRESUMO
AIMS: The middle-out perspective (MOP) provides a lens to examine how actors positioned between government (top) and individuals (bottom) act to promote broader societal changes from the middle-out (rather than the top-down or bottom-up). The MOP has been used in recent years in the fields of energy, climate change, and development studies. We argue that public health practitioners involved with advocacy activities and creating alliances to amplify health promotion actions will be familiar with the general MOP concept if not the formal name. The article aims to demonstrate this argument. METHODS: This article introduces the MOP conceptual framework and customises it for a public health audience by positioning it among existing concepts and theories for actions within public health. Using two UK case studies (increasing signalised crossing times for pedestrians and the campaign for smoke-free legislation), we illustrate who middle actors are and what they can do to result in better public health outcomes. RESULTS: These case studies show that involving a wider range of middle actors, including those not traditionally involved in improving the public's health, can broaden the range and reach of organisations and individuals involving in advocating for public health measures. They also demonstrate that middle actors are not neutral. They can be recruited to improve public health outcomes, but they may also be exploited by commercial interests to block healthy policies or even promote a health-diminishing agenda. CONCLUSION: Using the MOP as a formal approach can help public health organisations and practitioners consider potential 'allies' from outside traditional health-related bodies or professions. Formal mapping can expand the range of who are considered potential middle actors for a particular public health issue. By applying the MOP, public health organisations and staff can enlist the additional leverage that is brought to bear by involving additional middle actors in improving the public's health.
RESUMO
Three-dimensional (3D) cellular aggregates, termed spheroids, have become the forefront of in vitro cell culture in recent years. In contrast to culturing cells as two-dimensional, single-cell monolayers (2D culture), spheroid cell culture promotes, regulates, and supports physiological cellular architecture and characteristics that exist in vivo, including the expression of extracellular matrix proteins, cell signaling, gene expression, protein production, differentiation, and proliferation. The importance of 3D culture has been recognized in many research fields, including oncology, diabetes, stem cell biology, and tissue engineering. Over the last decade, improved methods have been developed to produce spheroids and assess their metabolic function and fate. Extracellular flux (XF) analyzers have been used to explore mitochondrial function in 3D microtissues such as spheroids using either an XF24 islet capture plate or an XFe96 spheroid microplate. However, distinct protocols and the optimization of probing mitochondrial energy metabolism in spheroids using XF technology have not been described in detail. This paper provides detailed protocols for probing mitochondrial energy metabolism in single 3D spheroids using spheroid microplates with the XFe96 XF analyzer. Using different cancer cell lines, XF technology is demonstrated to be capable of distinguishing between cellular respiration in 3D spheroids of not only different sizes but also different volumes, cell numbers, DNA content and type. The optimal mitochondrial effector compound concentrations of oligomycin, BAM15, rotenone, and antimycin A are used to probe specific parameters of mitochondrial energy metabolism in 3D spheroids. This paper also discusses methods to normalize data obtained from spheroids and addresses many considerations that should be considered when exploring spheroid metabolism using XF technology. This protocol will help drive research in advanced in vitro spheroid models.
Assuntos
Técnicas de Cultura de Células , Esferoides Celulares , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Metabolismo Energético , Mitocôndrias/metabolismoRESUMO
BACKGROUND: Interleukin (IL)-25 (IL-17E) is a potent inducer of the type-2 immune effector response. Previously we have demonstrated that a neutralizing anti-IL-25 antibody, given during the establishment of ovalbumin-specific lung allergy, abrogates airways hyperreactivity. OBJECTIVE: Blocking IL-25 results in the suppression of IL-13, a cytokine known to exacerbate pulmonary inflammation, and an unexpected reciprocal increase in IL-17A. The role of IL-17A in asthma is complex with reports of both pro-inflammatory and anti-inflammatory functions. Our aim was to determine the influence of IL-17A in regulating IL-25-dependent lung allergy. METHOD: Neutralizing antibodies to IL-25 and/or IL-17A were administered during an experimental model of allergic asthma. Bronchoalveolar cell infiltrates and lung cytokine production were determined to assess lung inflammation. Invasive plethysmography was undertaken to measure lung function. RESULTS: Neutralization of IL-25 correlated with a decrease in IL-13 levels and an increase in IL-17A production, and an accompanying prevention of airway hyperresponsiveness (AHR). Notably, the blocking of IL-17A reversed the protective effects of treating with anti-IL-25 antibodies, resulting in the re-expression of several facets of the lung inflammatory response, including IL-13 and eotaxin production, eosinophilia and AHR. Using mice over-expressing IL-13 we demonstrate that treatment of these mice with anti-IL-25 fails to suppress IL-13 levels and in turn IL-17A levels remain suppressed. CONCLUSIONS AND CLINICAL RELEVANCE: IL-13 is known to be an important inducer of lung inflammation, causing goblet cell hyperplasia and promoting airways hyperreactivity. Our data now demonstrate that IL-13 also plays an important role in the genesis of lung inflammation downstream of IL-25 by suppressing a protective IL-17A response. These findings also highlight the important reciprocal interplay of the IL-17 family members, IL-25 and IL-17A, in regulating allergic lung responses and suggest that the balance of IL-17A, together with IL-25, will be an important consideration in the treatment of allergic asthma.
Assuntos
Hiper-Reatividade Brônquica/imunologia , Interleucina-13/metabolismo , Interleucina-17/metabolismo , Hipersensibilidade Respiratória/imunologia , Animais , Asma/imunologia , Asma/metabolismo , Asma/fisiopatologia , Citocinas/biossíntese , Citocinas/metabolismo , Feminino , Humanos , Pulmão/imunologia , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Ovalbumina/imunologia , Pneumonia/imunologia , Células Th2/imunologiaRESUMO
BACKGROUND: Initial studies suggested that polymorphisms in Tim1 and Tim3 contribute to the development of airway hyperreactivity (AHR) in an acute mouse model of asthma. This was also mirrored in human genetic studies where polymorphisms in Tim1 and Tim3 have been associated with atopic populations. OBJECTIVE: Further studies using anti-Tim1 or -Tim3 antibodies, or Tim fusion proteins, have also suggested that these molecules may function as regulators of type-1 and type-2 immunity. However, their role in the development of AHR and airway inflammation remains unclear. Given the proposed roles for Tim1 and Tim3 in type-1 and type-2 responses, we sought to determine whether these molecules were important in regulating antigen-driven lung allergy and inflammation. METHOD: We used Tim1- and Tim3-deficient mice and determined how the development of allergic lung inflammation was affected. RESULTS: AHR was induced normally in the absence of both Tim1 and Tim3, although Tim1-deficient mice did show a small but significant decrease in cell infiltration in the lung and blood eosinophilia. Although Tim3 was expressed on CD4(+) T cells in the allergic lung, Tim1 expression was restricted to CD86(+) B cells. CONCLUSIONS AND CLINICAL RELEVANCE: Thus, Tim1 and Tim3 are not essential for the induction of the type-2 response in lung allergy. This is contrary to what was proposed in a number of other studies using neutralizing and activating antibodies and questions the clinical relevance of Tim1 and Tim3 for novel allergy therapies.
Assuntos
Asma/metabolismo , Asma/fisiopatologia , Hipersensibilidade Imediata/metabolismo , Hipersensibilidade Imediata/fisiopatologia , Proteínas de Membrana/metabolismo , Receptores Virais/metabolismo , Animais , Asma/imunologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Antígeno B7-2/metabolismo , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/metabolismo , Hiper-Reatividade Brônquica/fisiopatologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Modelos Animais de Doenças , Receptor Celular 1 do Vírus da Hepatite A , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Hipersensibilidade Imediata/imunologia , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Pulmão , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Receptores Virais/deficiência , Receptores Virais/genéticaRESUMO
Because no detailed information exists regarding the topographic representation of swallowing musculature on the human cerebral cortex in health or disease, we used transcranial magnetic stimulation to study the cortical topography of human oral, pharyngeal and esophageal musculature in 20 healthy individuals and the topography of pharyngeal musculature in two stroke patients, one with and one without dysphagia. Our results demonstrate that swallowing musculature is discretely and somatotopically represented on the motor and premotor cortex of both hemispheres but displays interhemispheric asymmetry, independent of handedness. Following stroke, dysphagia appeared to be associated with smaller pharyngeal representation on the intact hemisphere, which increases in size with recovery of swallowing.
Assuntos
Transtornos Cerebrovasculares/fisiopatologia , Deglutição/fisiologia , Hemiplegia/fisiopatologia , Córtex Motor/fisiopatologia , Músculo Liso/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Adolescente , Adulto , Idoso , Mapeamento Encefálico , Eletromiografia , Esôfago/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Faringe/fisiopatologia , Reprodutibilidade dos Testes , Transdução de Sinais , Tomógrafos Computadorizados , Gêmeos MonozigóticosRESUMO
Biodiversity loss from deforestation may be partly offset by the expansion of secondary forests and plantation forestry in the tropics. However, our current knowledge of the value of these habitats for biodiversity conservation is limited to very few taxa, and many studies are severely confounded by methodological shortcomings. We examined the conservation value of tropical primary, secondary, and plantation forests for 15 taxonomic groups using a robust and replicated sample design that minimized edge effects. Different taxa varied markedly in their response to patterns of land use in terms of species richness and the percentage of species restricted to primary forest (varying from 5% to 57%), yet almost all between-forest comparisons showed marked differences in community structure and composition. Cross-taxon congruence in response patterns was very weak when evaluated using abundance or species richness data, but much stronger when using metrics based upon community similarity. Our results show that, whereas the biodiversity indicator group concept may hold some validity for several taxa that are frequently sampled (such as birds and fruit-feeding butterflies), it fails for those exhibiting highly idiosyncratic responses to tropical land-use change (including highly vagile species groups such as bats and orchid bees), highlighting the problems associated with quantifying the biodiversity value of anthropogenic habitats. Finally, although we show that areas of native regeneration and exotic tree plantations can provide complementary conservation services, we also provide clear empirical evidence demonstrating the irreplaceable value of primary forests.
Assuntos
Biodiversidade , Agricultura Florestal , Clima TropicalRESUMO
BACKGROUND: Infant growth and lifestyle are now recognized as being critical determinants of later obesity. EMPOWER (Empowering Parents to Prevent Obesity at Weaning: Exploratory Research) was developed as an intervention for parents whose babies are at high risk. Delivered by specially trained health visitors, it is underpinned by the Family Partnership Model and uses a strengths-based, solution-focused way of working with families. METHODS: Mothers of babies participating in the pilot of EMPOWER in Leeds were recruited to take part in a study to examine perceptions about the programme's acceptability and usefulness. Interviews were taped and transcribed, and thematic analysis undertaken. RESULTS: Families talked positively about the approach of the EMPOWER health visitor with her emphasis on listening, partnership working and shared problem-solving. Parents particularly valued the use of a non-judgemental approach, which they felt had helped them to discuss openly, sensitive issues such as weight and diet. They identified a number of important benefits ranging from increased knowledge about the most appropriate types and amount of food to feed their toddler, to more far-reaching changes within the family as a whole, including modifications to their own diet and lifestyle. Programmes of this nature were perceived as more valuable than the standard help that is currently available. CONCLUSION: The EMPOWER programme appears to be both acceptable and valued by targeted parents and a potentially effective means of supporting high-risk families to prevent their children from developing obesity. An exploratory randomized controlled trial is now underway to ascertain the feasibility of conducting a definitive phase 3 trial.