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The Bacopa monnieri plant contains phytochemicals that have been used extensively in traditional medicine to treat various diseases. More recently it has been shown to accelerate wound healing, though its mechanism of action is largely unknown. Here we investigated the cellular pathways activated by a methanol extract of Bacopa monnieri in human dermal fibroblasts, which play many critical roles in the wound healing program. Gene expression analysis revealed that the Bacopa monnieri extract can modulate multiple processes involved in the wound healing program such as migration, proliferation, and angiogenesis. We discovered that the extract can increase migration of fibroblasts via modulating the size and number of focal adhesions. Bacopa monnieri-mediated changes in focal adhesions are dependent on α5ß1 integrin activation and subsequent phosphorylation of focal adhesion kinase (FAK). Altogether our results suggest that Bacopa monnieri extract could enhance the wound healing rate via modulating fibroblast migration into the wound bed.
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Importance: Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer. Objective: To determine whether selenium and/or vitamin E may prevent disease recurrence in patients with newly diagnosed NMIBC. Design, Setting, and Participants: This multicenter, prospective, double-blinded, placebo-controlled, 2 × 2 factorial randomized clinical trial included patients with newly diagnosed NMIBC recruited from 10 secondary or tertiary care hospitals in the UK. A total of 755 patients were screened for inclusion; 484 did not meet the inclusion criteria, and 1 declined to participate. A total of 270 patients were randomly assigned to 4 groups (selenium plus placebo, vitamin E plus placebo, selenium plus vitamin E, and placebo plus placebo) in a double-blind fashion between July 17, 2007, and October 10, 2011. Eligibility included initial diagnosis of NMIBC (stages Ta, T1, or Tis); randomization within 12 months of first transurethral resection was required. Interventions: Oral selenium (200 µg/d of high-selenium yeast) and matched vitamin E placebo, vitamin E (200 IU/d of d-alfa-tocopherol) and matched selenium placebo, selenium and vitamin E, or placebo and placebo. Main Outcome and Measures: Recurrence-free interval (RFI) on an intention-to-treat basis (analyses completed on November 28, 2022). Results: The study randomized 270 patients (mean [SD] age, 68.9 [10.4] years; median [IQR] age, 69 [63-77] years; 202 male [75%]), with 65 receiving selenium and vitamin E placebo, 71 receiving vitamin E and selenium placebo, 69 receiving selenium and vitamin E, and 65 receiving both placebos. Median overall follow-up was 5.5 years (IQR, 5.1-6.1 years); 228 patients (84%) were followed up for more than 5 years. Median treatment duration was 1.5 years (IQR, 0.9-2.5 years). The study was halted because of slow accrual. For selenium (n = 134) vs no selenium (n = 136), there was no difference in RFI (hazard ratio, 0.92; 95% CI, 0.65-1.31; P = .65). For vitamin E (n = 140) vs no vitamin E (n = 130), there was a statistically significant detriment to RFI (hazard ratio, 1.46; 95% CI, 1.02-2.09; P = .04). No significant differences were observed for progression-free interval or overall survival time with either supplement. Results were unchanged after Cox proportional hazards regression modeling to adjust for known prognostic factors. In total, 1957 adverse events were reported; 85 were serious adverse events, and all were considered unrelated to trial treatment. Conclusions and Relevance: In this randomized clinical trial of selenium and vitamin E, selenium supplementation did not reduce the risk of recurrence in patients with NMIBC, but vitamin E supplementation was associated with an increased risk of recurrence. Neither selenium nor vitamin E influenced progression or overall survival. Vitamin E supplementation may be harmful to patients with NMIBC, and elucidation of the underlying biology is required. Trial Registration: isrctn.org Identifier: ISRCTN13889738.
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Neoplasias não Músculo Invasivas da Bexiga , Selênio , Neoplasias da Bexiga Urinária , Humanos , Masculino , Idoso , Vitamina E/uso terapêutico , Selênio/uso terapêutico , Estudos Prospectivos , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias da Bexiga Urinária/prevenção & controle , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
Dog owners are often impressed by their dog's sense of smell. Many of these dogs, however, have skulls that are quite altered from those of their closest canid relatives. Housed within these skulls are essential olfactory structures like the cribriform plate that play a role in olfaction and the transmission of olfactory nerve impulses to the olfactory bulb of the brain. With improvements in CT technology and accessibility, we are now able to digitally reconstruct in 3D cribriform plate morphology and study its variation within and among species. In this study, we CT scanned the skulls of 95 dog specimens from 45 different domestic dog breeds and 12 species of wild canid and compared the shape of the cribriform plate among three main groups: domestic dog breeds, wolf-like canids, and fox-like canids. Despite only recent selective pressure for extreme skull morphology, domestic dogs display much more variation in cribriform plate shape than wild canids, indicating that cribriform plate shape is plastic and linked to skull shape. Intense artificial selection on domestic dog skull phenotype in the last 200 years has clear effects on secondary features of the domestic dog skull, implying that selection for overt phenotypes also can impact other anatomical features associated with the skull, like the cribriform plate.
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Cães/anatomia & histologia , Osso Etmoide/anatomia & histologia , Crânio/anatomia & histologia , Olfato/fisiologia , Lobos/anatomia & histologia , Animais , Evolução Biológica , Cães/fisiologia , Osso Etmoide/diagnóstico por imagem , Fenótipo , Crânio/diagnóstico por imagemRESUMO
The domestic dog is assumed by nearly everyone to be the consummate smeller. Within the species Canis familiaris individual breeds, such as the bloodhound or beagle, are known as olfactory stars. These are "scent breeds," a grouping variably defined as a genetic clade or breed class commonly used for scent detection tasks. Previous work suggests that the dog has a more robust olfactory anatomy than many mammal species. Now we undertake a closer investigation of the dog's olfactory system, both in relationship to its closest wild relatives, the wolf and coyote, and across individual breeds. First, we seek to resolve whether the dog has lost olfactory capacity through its domestication from the wolf lineage. Second, we test the inertial lore that among dogs, "scent breeds," have a superior olfactory facility. As a measure of relative olfactory capacity, we look to the cribriform plate (CP), a bony cup in the posterior nasal cavity perforated by passageways for all olfactory nerve bundles streaming from the periphery to the brain. Using high-resolution computed tomography (CT) scans and digital quantification, we compare relative CP size in 46 dog breeds, the coyote and gray wolf. Results show the dog has a reduced CP surface area relative to the wolf and coyote. Moreover, we found no significant differences between CP size of "scent" and "non-scent" breeds. Our study suggests that the dog lost olfactory capacity as a result of domestication and this loss was not recovered in particular breed groupings through directed artificial selection for increased olfactory facility.
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Cães/anatomia & histologia , Domesticação , Osso Etmoide/anatomia & histologia , Olfato/fisiologia , Lobos/anatomia & histologia , Animais , Cães/fisiologia , Especificidade da Espécie , Lobos/fisiologiaRESUMO
BACKGROUND: To describe how using a combined approach of community-based participatory research and intervention mapping principles could inform the development of a tailored complex intervention to improve management of asthma for South Asian (SA) children; Management and Interventions for Asthma (MIA) study. METHODS: A qualitative study using interviews, focus groups, workshops, and modified intervention mapping procedures to develop an intervention planning framework in an urban community setting in Leicester, UK. The modified form of intervention mapping (IM) included: systematic evidence synthesis; community study; families and healthcare professionals study; and development of potential collaborative intervention strategies. Participants in the community study were 63 SA community members and 12 key informants; in-depth semi-structured interviews involved 30 SA families, 14 White British (WB) families and 37 Healthcare Professionals (HCPs) treating SA children living with asthma; prioritisation workshops involved 145 SA, 6 WB and 37 HCP participants; 30 participants in finalisation workshops. RESULTS: Two key principles were utilised throughout the development of the intervention; community-based participatory research (CBPR) principles and intervention mapping (IM) procedures. The CBPR approach allowed close engagement with stakeholders and generated valuable knowledge to inform intervention development. It accounted for diverse perceptions and experiences with regard to asthma and recognised the priorities of patients and their families/caregivers for service improvement. The 'ACT on Asthma' programme was devised, comprising four arms of an intervention strategy: education and training, clinical support, advice centre and raising awareness, to be co-ordinated by a central team. CONCLUSIONS: The modified IM principles utilised in this study were systematic and informed by theory. The combined IM and participatory approach could be considered when tailoring interventions for other clinical problems within diverse communities. The IM approach to intervention development was however resource intensive. Working in meaningful collaboration with minority communities requires specific resources and a culturally competent methodology.
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Asma , População Branca , Asma/terapia , Criança , Pesquisa Participativa Baseada na Comunidade , Grupos Focais , Humanos , Pesquisa QualitativaRESUMO
It is widely accepted that obligate aquatic mammals, specifically toothed whales, rely relatively little on olfaction. There is less agreement about the importance of smell among aquatic mammals with residual ties to land, such as pinnipeds and sea otters. Field observations of marine carnivorans stress their keen use of smell while on land or pack ice. Yet, one dimension of olfactory ecology is often overlooked: while underwater, aquatic carnivorans forage "noseblind," diving with nares closed, removed from airborne chemical cues. For this reason, we predicted marine carnivorans would have reduced olfactory anatomy relative to closely related terrestrial carnivorans. Moreover, because species that dive deeper and longer forage farther removed from surface scent cues, we predicted further reductions in their olfactory anatomy. To test these hypotheses, we looked to the cribriform plate (CP), a perforated bone in the posterior nasal chamber of mammals that serves as the only passageway for olfactory nerves crossing from the periphery to the olfactory bulb and thus covaries in size with relative olfactory innervation. Using CT scans and digital quantification, we compared CP morphology across Arctoidea, a clade at the interface of terrestrial and aquatic ecologies. We found that aquatic carnivoran species from two lineages that independently reinvaded marine environments (Pinnipedia and Mustelidae), have significantly reduced relative CP than terrestrial species. Furthermore, within these aquatic lineages, diving depth and duration were strongly correlated with CP loss, and the most extreme divers, elephant seals, displayed the greatest reductions. These observations suggest that CP reduction in carnivorans is an adaptive response to shifting selection pressures during secondary invasion of marine environments, particularly to foraging at great depths. Because the CP is fairly well preserved in the fossil record, using methods presented here to quantify CP morphology in extinct species could further clarify evolutionary patterns of olfactory loss across aquatic mammal lineages that have independently committed to life in water.
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OBJECTIVE: This paper draws on the data from the Management and Interventions for Asthma (MIA) study to explore the perceptions and experiences of asthma in British South Asian children using semi-structured interviews. A comparable cohort of White British children was recruited to identify whether any emerging themes were subject to variation between the two groups so that generic and ethnicity-specific themes could be identified for future tailored intervention programmes for South Asian children with asthma. SETTING: South Asian and White British children with asthma took part in semi-structured interviews in Leicester, UK. PARTICIPANTS: Thirty three South Asian and 14 White British children with asthma and aged 5-12 years were interviewed. RESULTS: Both similar and contrasting themes emerged from the semi-structured interviews. Interviews revealed considerable similarities in the experience of asthma between the South Asian and White British children, including the lack of understanding of asthma (often confusing trigger with cause), lack of holistic discussions with healthcare professionals (HCPs), an overall neutral or positive experience of interactions with HCPs, the role of the family in children's self-management and the positive role of school and friends. Issues pertinent to South Asian children related to a higher likelihood of feeling embarrassed and attributing physical activity to being a trigger for asthma symptoms. CONCLUSIONS: The two ethnicity-specific factors revealed by the interviews are significant in children's self-management of asthma and therefore, indicate the need for a tailored intervention in South Asian children.
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Povo Asiático , Asma , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Relações Médico-Paciente , Autogestão , População Branca , Bangladesh , Criança , Pré-Escolar , Feminino , Humanos , Índia , Masculino , Paquistão , Educação Física e Treinamento , Pesquisa Qualitativa , Instituições Acadêmicas , Esportes , Reino UnidoRESUMO
The evolution of mammalian olfaction is manifested in a remarkable diversity of gene repertoires, neuroanatomy and skull morphology across living species. Olfactory receptor genes (ORGs), which initiate the conversion of odorant molecules into odour perceptions and help an animal resolve the olfactory world, range in number from a mere handful to several thousand genes across species. Within the snout, each of these ORGs is exclusively expressed by a discrete population of olfactory sensory neurons (OSNs), suggesting that newly evolved ORGs may be coupled with new OSN populations in the nasal epithelium. Because OSN axon bundles leave high-fidelity perforations (foramina) in the bone as they traverse the cribriform plate (CP) to reach the brain, we predicted that taxa with larger ORG repertoires would have proportionately expanded footprints in the CP foramina. Previous work found a correlation between ORG number and absolute CP size that disappeared after accounting for body size. Using updated, digital measurement data from high-resolution CT scans and re-examining the relationship between CP and body size, we report a striking linear correlation between relative CP area and number of functional ORGs across species from all mammalian superorders. This correlation suggests strong developmental links in the olfactory pathway between genes, neurons and skull morphology. Furthermore, because ORG number is linked to olfactory discriminatory function, this correlation supports relative CP size as a viable metric for inferring olfactory capacity across modern and extinct species. By quantifying CP area from a fossil sabertooth cat (Smilodon fatalis), we predicted a likely ORG repertoire for this extinct felid.
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Osso Etmoide/anatomia & histologia , Mamíferos/anatomia & histologia , Mamíferos/fisiologia , Receptores Odorantes/genética , Olfato/fisiologia , Animais , Mamíferos/genética , Receptores Odorantes/metabolismo , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Over one million children receive treatment for asthma in the UK. South Asian children experience excess morbidity and higher rates of hospitalization than the White population. This study aimed to explore perceptions and experiences of asthma and asthma management in British South Asian and White British families, to identify barriers to optimal management and to inform culturally appropriate interventions to improve management. METHODS: A qualitative methodology, using semi-structured interviews was adopted. Members of 30 families from six major South Asian ethnic-religious groups were purposively sampled (n = 49). For comparison, 17 White British parents were interviewed. Topics included understandings of asthma; day-to-day management; interactions with health care providers and the perceived quality of healthcare services. Data were analyzed using interpretive thematic analysis, facilitated by NVivo. Similarities and differences between South Asian and White families were analysed across key themes. RESULTS: Many of the problems facing families of a child with asthma were common to South Asian and White British families. Both had limited understanding of asthma causes and triggers and expressed confusion about the use of medications. Both groups reported delays in receiving a clear diagnosis and many experienced what was perceived as uncoordinated care and inconsistent advice from health professionals. No family had received an asthma plan. South Asian families had more difficulty in recognising severity of symptoms and those with limited English faced additional barriers to receiving adequate information and advice about management due to poor communication support systems. South Asian parents reported higher levels of involvement of wider family and higher levels of stigma. Attendance at the emergency department was related to previous experience, difficulties in accessing primary care, lack of knowledge of alternatives and difficulties in assessing severity. CONCLUSIONS: Barriers to optimal asthma management exist at the individual family, community and healthcare systems levels. Culturally sensitive, holistic and collaboratively designed interventions are needed. Improved communication support for families with lower proficiency in English is required. Healthcare professionals need to ensure that families receive an asthma plan and make greater efforts to check families' understandings of asthma triggers, use of medications, assessment of asthma severity and accessing help.
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Povo Asiático/psicologia , Asma/terapia , Conhecimentos, Atitudes e Prática em Saúde , Pais/psicologia , População Branca/psicologia , Antiasmáticos/efeitos adversos , Criança , Pré-Escolar , Gerenciamento Clínico , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pesquisa Qualitativa , Reino UnidoRESUMO
The small, perforated bony cup of the anterior cranial fossa called the cribriform plate (CP) is perhaps the best-preserved remnant of olfactory anatomy in fossil mammal skulls. The CP and its myriad foramina record the passage of peripheral olfactory nerves from nasal cavity to olfactory bulb. Previous work has suggested that CP surface area reflects aspects of olfactory capacity (as inferred from habitat and observed behavior) in mammals. To further explore the utility of CP as a proxy for olfactory function, we designed novel, nondestructive digital methods to quantify CP morphology from dry skulls. Using CT scans and 3-D imaging software, we quantified CP features from 42 species of Carnivora, a group that represents a wide spectrum of ecologies and sensory demands. Two metrics, CP surface area (CPSA) and cumulative CP foramina area (FXSA), scaled to skull length with negative allometry, and differed between aquatic and terrestrial species, with the former having reduced areas. Number of foramina (NF) was not correlated with skull length but tended to be greater in caniforms than feliforms. Both CPSA and FXSA are well correlated with ethmoturbinal surface area, a known osteological correlate of olfactory function. This suggests that CPSA and FXSA are useful proxies for olfactory ability, especially when studying fossils or skulls in which turbinals are not preserved. Total area of CP foramina (FXSA), an exacting measure of olfactory nerve endocasts, is tightly correlated with CPSA. Because of this, it may be desirable to use CPSA alone as a proxy given that it is easier to measure than FXSA.
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Carnívoros/anatomia & histologia , Carnívoros/fisiologia , Osso Etmoide/anatomia & histologia , Osso Etmoide/fisiologia , Filogenia , Animais , Feminino , Masculino , Cavidade Nasal/anatomia & histologia , Cavidade Nasal/fisiologia , Crânio/anatomia & histologia , Especificidade da EspécieRESUMO
To enhance bite force at the canines, feliform carnivorans have short rostra relative to caniform carnivorans. Rostral reduction in feliforms results in less rostrocaudal space for the maxilloturbinals, the complex set of bones involved in conditioning inspired air and conserving water. It is unknown whether the maxilloturbinals might show adaptations to adjust for this loss, such as greater complexity than what is observed in longer snouted caniforms. To understand the impact of rostral shortening on turbinals in feliforms, we used high resolution CT scans to quantify turbinal surface areas (SA) in 16 feliforms and compared them with published data on 20 caniforms. Results indicate that feliforms have reduced maxilloturbinal SA for their body mass relative to caniforms, but comparable fronto-ethmoturbinal SA. However, anterior portions of the ethmoturbinals in feliforms extend forward into the snout and are positioned within the respiratory pathway. When the SA of these anterior ethmoturbinals is added to maxilloturbinal SA to produce an estimated respiratory SA, feliforms and caniforms are similar in respiratory SA. This transfer of ethmoturbinal SA to respiratory function results in feliforms having less estimated olfactory SA relative to caniforms. Previous work on canids found a positive association between olfactory surface area and diet, but this was not found for felids. Results are consistent with feliforms having somewhat reduced olfactory ability relative to caniforms. If confirmed by behavioral data, the relative reduction in olfactory SA in many feliforms may reflect a greater reliance on vision in foraging relative to caniforms.
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Carnívoros/anatomia & histologia , Carnívoros/fisiologia , Cavidade Nasal/anatomia & histologia , Cavidade Nasal/fisiologia , Respiração , Olfato/fisiologia , Animais , Nariz/anatomia & histologia , Nariz/fisiologiaRESUMO
BACKGROUND: South Asian children with asthma are less likely to receive prescriptions and more likely to suffer uncontrolled symptoms and acute asthma admissions compared with White British children. Understanding barriers are therefore vital in addressing health inequalities. We undertook a systematic review identifying explanatory factors for barriers and facilitators to asthma management in South Asian children. South Asians were defined as individuals of Indian, Pakistani or Bangladeshi descent. METHODS: Data Sources - Medline, HMIC, EMBASE, ASSIA, Web of Science, BNI, CINAHL, PsycINFO, OpenSIGLE, CRD, Scopus, NHS Evidence, Cochrane Library, Campbell Collaboration, RCPCH, ATS, ERS, Asthma UK, Google Scholar & Asthma Guidelines (BTS, GINA, ATS, Monash, NAEPP, Singapore & New Zealand) to August 2013.Inclusion Criteria - Qualitative, quantitative or mixed methods research with primary focus on identifying explanations for barriers and/or facilitators to asthma management in South Asian children aged 0-18 years with diagnosed/suspected asthma and/or carers and/or healthcare professionals.Data Extraction - Three authors independently reviewed, selected & extracted eligible articles with disagreements resolved by research team discussion. RESULTS: 15 studies encompassing 25,755 children, 18,483 parents/carers and 239 healthcare professionals were included. Barriers and explanatory factors identified were:1. Lack of asthma knowledge in families and healthcare professionals.2. Under-use of preventer medications.3. Non-acceptance/denial of asthma.4. Over-reliance on Emergency Department management.5. Communication problems.6. Non-adherence to medication.7. Use of complementary therapies.Little facilitators regarding asthma management were identified. CONCLUSIONS: Several key issues were identified as likely to be ethnic-specific to South Asian families, rather than a reflection of minority status: impact of parental and professional knowledge and beliefs, health service utilisation pattern explanations and the impact of prejudice and stigmatisation. Other explanations such as language barriers are not strictly ethnic specific but instead reflect a minority position.Further research is required to identify why barriers exist, the mechanisms by which they impact on asthma management and how they can be overcome. Furthermore, understanding the difference between barriers and explanations that are ethnic-specific and those that are related to being a minority will enable the application of generic system-wide interventions where ethnicity is not the issue and ethnically-tailored interventions where needed.
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Asma/prevenção & controle , Barreiras de Comunicação , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Asma/etnologia , Bangladesh , Criança , Proteção da Criança , Pré-Escolar , Feminino , Disparidades em Assistência à Saúde , Humanos , Índia , Lactente , Recém-Nascido , Masculino , Paquistão , Educação de Pacientes como AssuntoRESUMO
The defensive slime of hagfishes contains thousands of intermediate filament protein threads that are manufactured within specialized gland thread cells. The material properties of these threads rival those of spider dragline silks, which makes them an ideal model for biomimetic efforts to produce sustainable protein materials, yet how the thread is produced and organized within the cell is not well understood. Here we show how changes in nuclear morphology, size and position can explain the three-dimensional pattern of thread coiling in gland thread cells, and how the ultrastructure of the thread changes as very young thread cells develop into large cells with fully mature coiled threads. Our model provides an explanation for the complex process of thread assembly and organization that has fascinated and perplexed biologists for over a century, and provides valuable insights for the quest to manufacture high-performance biomimetic protein materials.
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Estruturas Animais/citologia , Proteínas de Peixes/ultraestrutura , Feiticeiras (Peixe)/metabolismo , Proteínas de Filamentos Intermediários/química , Estruturas Animais/metabolismo , Estruturas Animais/ultraestrutura , Animais , Proteínas de Peixes/metabolismo , Feiticeiras (Peixe)/citologia , Feiticeiras (Peixe)/ultraestrutura , Proteínas de Filamentos Intermediários/metabolismo , Proteínas de Filamentos Intermediários/ultraestruturaRESUMO
OBJECTIVES: To compare patient and tumour characteristics at presentation from two large bladder cancer cohorts, with recruitment separated by 15-20 years To identify significant differences in the West Midlands' urothelial cancer of the bladder (UCB) population during this period. PATIENTS AND METHODS: Data were collected prospectively from 1478 patients newly diagnosed with UCB in the West Midlands from January 1991 to June 1992 (Cohort 1), and from 1168 patients newly diagnosed with UBC within the same region from December 2005 to April 2011 (Cohort 2). Gender, age, smoking history, and tumour grade, stage, type, multiplicity and size at presentation were compared using a Pearson chi-square test or Cochran-Armitage trend test, as appropriate. RESULT: Cohort 2 had a higher proportion of male patients (P = 0.021), elderly patients (P < 0.001), grade 3 tumours (P < 0.001), Ta/T1 tumours (P = 0.008), multiple tumours (P < 0.001), and tumours of ≤2 cm in diameter (P < 0.001). CONCLUSIONS: There were significant differences between the cohorts. These differences are potentially explained by an ageing population, changes in grading practices, improved awareness of important symptoms, improved cystoscopic technology, and reductions in treatment delays. Regional cohorts remain important for identifying changes in tumour and patient characteristics that may influence disease management in the UK and beyond.
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Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Reino UnidoRESUMO
Involvement of service users in decision making, in both clinical and research settings, has become a central feature of many health and research funding policies in the last 15 years. Over the same timeframe, there has been an increasing focus on children's rights, promoted by the UN Convention of the Rights of the Child, which gives children a right to be involved in decisions that affect their lives. In a research setting, this has resulted in increased engagement of children in research, as opposed to relying on parents or carers to represent their children, and a shift from research on children to research with children. In this article, we discuss collaboration with children under the age of 16 years in health research: what this means and why (or why not) to do it. The definition of collaboration is discussed and the lines among collaboration, involvement, participation and participatory research considered. The risks and benefits of collaboration are reviewed, both theoretical and evidence based, where evidence exists. The review ends with a look towards the future including the need for agreed definitions, better reporting of collaboration and other patient and public involvement activities with children to build up the much needed evidence base, the need for cost-benefit evaluations and, most importantly, the need for careful consideration as to whether collaborating with children is appropriate in each circumstance.
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Tomada de Decisões , Pesquisa sobre Serviços de Saúde/organização & administração , Benchmarking , Criança , Comportamento Cooperativo , Tomada de Decisões/ética , Ética em Pesquisa , Pesquisa sobre Serviços de Saúde/ética , Humanos , Projetos de PesquisaRESUMO
Within the nasal cavity of mammals is a complex scaffold of paper-thin bones that function in respiration and olfaction. Known as turbinals, the bones greatly enlarge the surface area available for conditioning inspired air, reducing water loss, and improving olfaction. Given their functional significance, the relative development of turbinal bones might be expected to differ among species with distinct olfactory, thermoregulatory and/or water conservation requirements. Here we explore the surface area of olfactory and respiratory turbinals relative to latitude and diet in terrestrial Caniformia, a group that includes the canid and arctoid carnivorans (mustelids, ursids, procyonids, mephitids, ailurids). Using high-resolution computed tomography x-ray scans, we estimated respiratory and olfactory turbinal surface area and nasal chamber volume from three-dimensional virtual models of skulls. Across the Caniformia, respiratory surface area scaled isometrically with estimates of body size and there was no significant association with climate, as estimated by latitude. Nevertheless, one-on-one comparisons of sister taxa suggest that arctic species may have expanded respiratory turbinals. Olfactory surface area scaled isometrically among arctoids, but showed positive allometry in canids, reflecting the fact that larger canids, all of which are carnivorous, had relatively greater olfactory surface areas. In addition, among the arctoids, large carnivorous species such as the polar bear (Ursus maritimus) and wolverine (Gulo gulo) also displayed enlarged olfactory turbinals. More omnivorous caniform species that feed on substantial quantities of non-vertebrate foods had less expansive olfactory turbinals. Because large carnivorous species hunt widely dispersed prey, an expanded olfactory turbinal surface area may improve a carnivore's ability to detect prey over great distances using olfactory cues.
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Carnívoros/anatomia & histologia , Modelos Anatômicos , Respiração , Olfato/fisiologia , Conchas Nasais/anatomia & histologia , Animais , Comportamento Apetitivo/fisiologia , Pesos e Medidas Corporais , Carnívoros/fisiologia , Dieta , Feminino , Masculino , Filogenia , Especificidade da Espécie , Tomografia Computadorizada por Raios X , Conchas Nasais/fisiologiaRESUMO
Inside the mammalian nose lies a labyrinth of bony plates covered in epithelium collectively known as turbinates. Respiratory turbinates lie anteriorly and aid in heat and water conservation, while more posterior olfactory turbinates function in olfaction. Previous observations on a few carnivorans revealed that aquatic species have relatively large, complex respiratory turbinates and greatly reduced olfactory turbinates compared with terrestrial species. Body heat is lost more quickly in water than air and increased respiratory surface area likely evolved to minimize heat loss. At the same time, olfactory surface area probably diminished due to a decreased reliance on olfaction when foraging under water. To explore how widespread these adaptations are, we documented scaling of respiratory and olfactory turbinate surface area with body size in a variety of terrestrial, freshwater, and marine carnivorans, including pinnipeds, mustelids, ursids, and procyonids. Surface areas were estimated from high-resolution CT scans of dry skulls, a novel approach that enabled a greater sampling of taxa than is practical with fresh heads. Total turbinate, respiratory, and olfactory surface areas correlate well with body size (r(2) ≥0.7), and are relatively smaller in larger species. Relative to body mass or skull length, aquatic species have significantly less olfactory surface area than terrestrial species. Furthermore, the ratio of olfactory to respiratory surface area is associated with habitat. Using phylogenetic comparative methods, we found strong support for convergence on 1:3 proportions in aquatic taxa and near the inverse in terrestrial taxa, indicating that aquatic mustelids and pinnipeds independently acquired similar proportions of olfactory to respiratory turbinates. Constraints on turbinate surface area in the nasal chamber may result in a trade-off between respiratory and olfactory function in aquatic mammals.
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Organismos Aquáticos/fisiologia , Carnívoros/anatomia & histologia , Conchas Nasais/anatomia & histologia , Animais , Organismos Aquáticos/classificação , Carnívoros/classificação , Filogenia , Tomografia Computadorizada por Raios XAssuntos
Fidelidade a Diretrizes , Guias de Prática Clínica como Assunto , Infecções Urinárias/diagnóstico , Criança , Competência Clínica , Educação de Pós-Graduação em Medicina , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Londres , Masculino , Corpo Clínico , Pediatria/educaçãoRESUMO
CONTEXT: Beginning in 1985, state-of-the-art surveys by the College of American Pathologists (CAP) led to M22-A guidelines by the National Committee for Clinical Laboratory Standards (NCCLS) for quality assurance (QA) of various commercially prepared isolation and diagnostic microbiology media. Some medium types were declared exempt from routine QA testing by each laboratory user, but manufacturer QA was maintained and specified in great detail. No update has occurred in more than 15 years as more complex media have been introduced into clinical microbiology practice. OBJECTIVE: To reassess the quality of commercially prepared microbiology media in the United States for the revision of NCCLS document M22-A2. Methods.-A questionnaire was designed to conform to that used by the CAP in 1985 and 1988, and was updated by lists of 52 recently introduced diagnostic media. Queries included details of laboratory QA in the last 12 months, such as number of lots tested, number of items in a lot, number of items in a quality control (QC) sample, number of lots failed, and reasons for lot failure. All CAP Microbiology Surveys participants received the document in late 2001. RESULTS: Data from nearly 300 000 media lots representing 32.7 million medium items were received from more than 3000 CAP Surveys subscribers. Lot raw data failure rates for all media ranged from 0.10% to 9.87% (average, 1.01%). Failures with media having a significant QC experience (> or =1000 lots or > or =100 000 items) adjusted for QC strain-based failures (so-called extrapolated failure rate) ranged from 0.04% to 1.34% (average, 0.40%). The threshold rate for QA exemption from 1985 analyses was expanded to 0.50% or less and now allows exemption of 27 media evaluated in this study. Local laboratory QA must remain in force (M22-A2) for the other 25 products. CONCLUSIONS: Generated QA failure results from the CAP Microbiology Surveys supplement recent results of the NCCLS M22 Subcommittee that will lead to more practical media QA guidelines and could significantly decrease costs for clinical microbiology laboratories through focusing QC on a smaller number of the most at-risk diagnostic products.