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1.
Clin Exp Immunol ; 211(3): 269-279, 2023 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-36622786

RESUMO

Cohorts of healthy younger adults (18-50yrs) and healthy older adults (60-75yrs) were immunized intramuscularly or intranasally with an adenovirus-vectored RSV vaccine (PanAd3-RSV) as a prime dose and boosted with PanAd3-RSV or a poxvirus-vectored vaccine (MVA-RSV) encoding the same insert. Whole blood gene expression was measured at baseline, 3- and 7-days post vaccination. Intramuscular prime vaccination with PanAd3-RSV induced differential expression of 643 genes (DEGs, FDR < 0.05). Intranasal prime vaccination with PanAd3-RSV did not induce any differentially expressed genes (DEGs) in blood samples at 3 days post vaccination. Intranasally primed participants showed greater numbers of DEGS on boosting than intramuscularly primed participants. The most highly enriched biological processes related to DEGs after both prime and boost vaccination were type-1 interferon related pathways, lymphocytic and humoral immune responses.


Assuntos
Pan troglodytes , Transcriptoma , Animais , Humanos , Idoso , Pan troglodytes/genética , Imunização Secundária , Vetores Genéticos/genética , Adenoviridae/genética , Anticorpos Antivirais
2.
Eur J Prosthodont Restor Dent ; 31(2): 92-103, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35917210

RESUMO

OBJECTIVES: To determine the success, survival, peri-implant health and prosthetic complications in head and neck cancer patients receiving oral rehabilitation utilising dental implants between 2008 and the present day. MATERIALS AND METHODS: Service evaluation. Survival Group: Retrospective review of records to determine implant survival and prosthetic complications. Success Group: Examination to determine implant success and health. RESULTS: Survival Group: 260 implants in 81 individuals, median follow up 49.2 months. 89.3% implant survival at 96 months, no further failures up to 133 months. 40.9% individuals required repair or remake of prosthesis by 72 months - mostly denture re-lines. Success group: 164 implants in 48 individuals, median follow up 56 months. Peri-implant mucositis detected in 22% of fixtures (37.5% individuals); peri-implantitis in 12.8% (25% individuals); 33.3% fixtures exhibiting periimplantitis at 120 months. Previous smoking significantly associated with development of peri-implantitis (HR 2.372, p=0.032, 95CI:1.232, 93.317). Compromised survival (e.g. peri-implantitis), absolute (not in mouth) or clinical failure estimated to occur in 28.1% fixtures at 101 months, mostly due to peri-implantitis. CONCLUSIONS: There is a large burden of ongoing care in this cohort, requiring interventions to improve peri-implant health and maintain complex prostheses. Oral rehabilitation and ongoing maintenance in this cohort is complex and multi-disciplinary.


Assuntos
Implantes Dentários , Neoplasias de Cabeça e Pescoço , Peri-Implantite , Humanos , Peri-Implantite/etiologia , Estudos Retrospectivos , Implantes Dentários/efeitos adversos , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/induzido quimicamente , Neoplasias de Cabeça e Pescoço/complicações
3.
Clin Radiol ; 76(2): 129-134, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33309335

RESUMO

AIM: To determine the proportion of renal cancers for which incidental detection was the route to diagnosis, the characteristics of tumours identified in this way, and the frequency with which opportunities to make this diagnosis were missed. MATERIALS AND METHODS: Consecutive patients with renal cancers treated at Royal Cornwall Hospitals NHS Trust (April 2011 and July 2018 inclusive) were identified from the Trust's cancer registry database, and a retrospective review of the imaging and electronic case notes was undertaken. Mann-Whitney U-tests for comparison of patient age and tumour size at diagnosis, and chi-squared tests for comparing cell type distribution and grade were performed. Logistic regression was then used to identify the characteristics of patients in whom a renal tumour was missed initially. RESULTS: Of 327 patients, 194 (63%) presented incidentally, and 133 (37%) symptomatically. Incidentally detected cancers were found in younger patients, (median of 65 years versus 69 p=0.01) and were smaller at presentation (median of 5.5 versus 7.2 cm, p<0.00001). Thirty-six different reporters missed opportunities to diagnose renal cancer in 50 (16%) patients on 78 occasions, 28 lesions (35%) being missed more than once. Thirty were imaged incompletely; four were visible only on a single image and three on a scout view at magnetic resonance imaging. CONCLUSION: The commonest route to diagnosis of renal cancer is by incidental detection of a mass. In 16% of patients in whom renal cancer is diagnosed, there is at least one prior examination on which the lesion is visible at an earlier date. The clinical impact of these missed diagnostic opportunities remains uncertain.


Assuntos
Erros de Diagnóstico/estatística & dados numéricos , Diagnóstico por Imagem/métodos , Achados Incidentais , Neoplasias Renais/diagnóstico por imagem , Idoso , Feminino , Humanos , Rim/diagnóstico por imagem , Masculino , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos
4.
Proc Natl Acad Sci U S A ; 115(22): 5726-5731, 2018 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-29760088

RESUMO

Lead pollution in Arctic ice reflects midlatitude emissions from ancient lead-silver mining and smelting. The few reported measurements have been extrapolated to infer the performance of ancient economies, including comparisons of economic productivity and growth during the Roman Republican and Imperial periods. These studies were based on sparse sampling and inaccurate dating, limiting understanding of trends and specific linkages. Here we show, using a precisely dated record of estimated lead emissions between 1100 BCE and 800 CE derived from subannually resolved measurements in Greenland ice and detailed atmospheric transport modeling, that annual European lead emissions closely varied with historical events, including imperial expansion, wars, and major plagues. Emissions rose coeval with Phoenician expansion, accelerated during expanded Carthaginian and Roman mining primarily in the Iberian Peninsula, and reached a maximum under the Roman Empire. Emissions fluctuated synchronously with wars and political instability particularly during the Roman Republic, and plunged coincident with two major plagues in the second and third centuries, remaining low for >500 years. Bullion in silver coinage declined in parallel, reflecting the importance of lead-silver mining in ancient economies. Our results indicate sustained economic growth during the first two centuries of the Roman Empire, terminated by the second-century Antonine plague.


Assuntos
Poluentes Ambientais , Gelo/análise , Chumbo , Mundo Romano/história , Conflitos Armados/história , Surtos de Doenças/história , Poluentes Ambientais/análise , Poluentes Ambientais/história , Indústrias Extrativas e de Processamento/história , Groenlândia , História Antiga , Humanos , Chumbo/análise , Chumbo/história , Prata/história
5.
Eur J Prosthodont Restor Dent ; 29(4): 209-217, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-33770422

RESUMO

Cracked tooth syndrome (CTS) is a common presentation in general practice. The diagnosis and management of teeth with CTS may be difficult due to the unknown extent of the crack. This article reviews the aetiology, diagnosis, management and prognosis of teeth with CTS. A thorough examination is required to effectively assess CTS. Intervention should aim to relieve symptoms and brace the remaining tooth structure effectively against further flexion. Restored teeth with CTS have a guarded prognosis due to the risk of further crack propagation, but the chances of survival at 5-years is acceptable (74.1-96.8%).


Assuntos
Síndrome de Dente Quebrado , Síndrome de Dente Quebrado/diagnóstico , Síndrome de Dente Quebrado/terapia , Humanos , Prognóstico
6.
Am J Bot ; 106(10): 1377-1385, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31553490

RESUMO

PREMISE: Hyperaccumulation of heavy metals in plants has never been documented from Central America or Mexico. Psychotria grandis, P. costivenia, and P. glomerata (Rubiaceae) have been reported to hyperaccumulate nickel in the Greater Antilles, but they also occur widely across the neotropics. The goals of this research were to investigate the geographic distribution of hyperaccumulation in these species and explore the phylogenetic distribution of hyperaccumulation in this clade by testing related species. METHODS: Portable x-ray fluorescence (XRF) spectroscopy was used to analyze 565 specimens representing eight species of Psychotria from the Missouri Botanical Garden herbarium. RESULTS: Nickel hyperaccumulation was found in specimens of Psychotria costivenia ranging from Mexico to Costa Rica and in specimens of P. grandis from Guatemala to Ecuador and Venezuela. Among related species, nickel hyperaccumulation is reported for the first time in P. lorenciana and P. papantlensis, but no evidence of hyperaccumulation was found in P. clivorum, P. flava, or P. pleuropoda. Previous reports of hyperaccumulation in P. glomerata appear to be erroneous, resulting from taxonomic synonymy and specimen misidentification. CONCLUSIONS: Hyperaccumulation of nickel by Psychotria is now known to occur widely from southern Mexico through Central America to northwestern South America, including some areas not known to have ultramafic soils. Novel aspects of this research include the successful prediction of new hyperaccumulator species based on molecular phylogeny, use of XRF technology to nondestructively obtain elemental data from herbarium specimens, and documentation of previously unknown areas of ultramafic or nickel-rich soil based on such data.


Assuntos
Psychotria , América Central , Costa Rica , México , Níquel , Filogenia , América do Sul
7.
Crit Rev Microbiol ; 44(1): 95-111, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28557577

RESUMO

The majority of invasive meningococcal disease (IMD) in the developed world is caused by capsular group B Neisseria meningitidis, however success with vaccination against organisms bearing this capsule has previously been restricted to control of geographically limited clonal outbreaks. As we enter a new era, with the first routine program underway to control endemic group B meningococcal disease for infants in the UK, it is timely to review the key landmarks in group B vaccine development, and discuss the issues determining whether control of endemic group B disease will be achieved. Evidence of a reduction in carriage acquisition of invasive group B meningococcal strains, after vaccination among adolescents, is imperative if routine immunization is to drive population control of disease beyond those who are vaccinated (i.e. through herd immunity). The need for multiple doses to generate a sufficiently protective response and reactogenicity remain significant problems with the new generation of vaccines. Despite these limitations, early data from the UK indicate that new group B meningococcal vaccines have the potential to have a major impact on meningococcal disease, and to provide new insight into how we might do better in the future.


Assuntos
Meningite Meningocócica/microbiologia , Vacinas Meningocócicas/imunologia , Neisseria meningitidis Sorogrupo B/imunologia , Animais , Humanos , Meningite Meningocócica/imunologia , Meningite Meningocócica/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Vacinas Meningocócicas/genética , Neisseria meningitidis Sorogrupo B/genética , Vacinação
8.
J Anat ; 230(3): 435-443, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27921302

RESUMO

The pectoral girdle is a complex structure which varies in its morphology between species. A major component in birds is the furcula, which can be considered equivalent to a fusion of the paired clavicles found in many mammals, and the single interclavicle found in many reptiles. These elements are a remnant of the dermal skeleton and the only intramembranous bones in the trunk. Postnatally, the furcula plays important mechanical roles by stabilising the shoulder joint and acting as a mechanical spring during flight. In line with its mechanical role, previous studies indicate that, unlike many other intramembranous bones, furcula growth during development can be influenced by mechanical stimuli. This study investigated the response of individual aspects of furcula growth to both embryo immobilisation and hypermotility in the embryonic chicken. The impact of altered incubation temperature, which influences embryo motility, on crocodilian interclavicle development was also explored. We employed whole-mount bone and cartilage staining and 3D imaging by microCT to quantify the impact of rigid paralysis, flaccid paralysis and hypermobility on furcula growth in the chicken, and 3D microCT imaging to quantify the impact of reduced temperature (32-28 °C) and motility on interclavicle growth in the crocodile. This revealed that the growth rates of the clavicular and interclavicular components of the furcula differ during normal development. Total furcula area was reduced by total unloading produced by flaccid paralysis, but not by rigid paralysis which maintains static loading of embryonic bones. This suggests that dynamic loading, which is required for postnatal bone adaptation, is not a requirement for prenatal furcula growth. Embryo hypermotility also had no impact on furcula area or arm length. Furcula 3D shape did, however, differ between groups; this was marked in the interclavicular component of the furcula, the hypocleideum. Hypocleideum length was reduced by both methods of immobilisation, and interclavicle area was reduced in crocodile embryos incubated at 28 °C, which are less motile than embryos incubated at 32 °C. These data suggest that the clavicular and interclavicle components of the avian furcula respond differently to alterations in embryo movement, with the interclavicle requiring both the static and dynamic components of movement-related loading for normal growth, while static loading preserved most aspects of clavicle growth. Our data suggest that embryo movement, and the mechanical loading this produces, is important in shaping these structures during development to suit their postnatal mechanical roles.


Assuntos
Jacarés e Crocodilos/embriologia , Desenvolvimento Ósseo , Osso e Ossos/embriologia , Embrião de Galinha/embriologia , Animais , Imageamento Tridimensional , Movimento , Microtomografia por Raio-X
9.
Sex Transm Infect ; 93(2): 105-111, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27535762

RESUMO

OBJECTIVES: To understand which aspects of general practitioner (GP) and HIV clinic appointments people living with HIV (PLWHIV) most value when seeking advice for new health problems. METHODS: A discrete choice experiment using a convenience sample of people diagnosed with HIV. Participants were recruited from 14 general HIV clinics in the South East of England between December 2014 and April 2015. ORs were calculated using conditional logit (CLOGIT) and latent class models (LCMs). RESULTS: A total of 1106 questionnaires were returned. Most participants were male (85%), white (74%) and were men who have sex with men (69%). The CLOGIT analysis showed people particularly valued shorter appointment waiting times (ORs between 1.52 and 3.62, p<0.001 in all instances). The LCM analysis showed there were two distinct classes, with 59% and 41% of respondents likely to be in each. The first class generally preferred GP to HIV clinic appointments and particularly valued 'being seen quickly'. For example, they had strong preferences for shorter appointment waiting times and longer GP opening hours. People in the second class also valued shorter waiting times, but they had a strong general preference for HIV clinic rather than GP appointments. CONCLUSIONS: PLWHIV value many aspects of care for new health problems, particularly short appointment waiting times. However, they appear split in their general willingness to engage with GPs.


Assuntos
Comportamento de Escolha , Infecções por HIV/terapia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Pesquisa sobre Serviços de Saúde , Preferência do Paciente/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Agendamento de Consultas , Inglaterra , Medicina Geral , Infecções por HIV/psicologia , Humanos , Preferência do Paciente/psicologia , Relações Médico-Paciente , Inquéritos e Questionários
10.
Heredity (Edinb) ; 118(1): 31-41, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27782119

RESUMO

Metal hyperaccumulation is an uncommon but highly distinctive adaptation found in certain plants that can grow on metalliferous soils. Here we review what is known about evolution of metal hyperaccumulation in plants and describe a population-genetic analysis of the Alyssum serpyllifolium (Brassicaceae) species complex that includes populations of nickel-hyperaccumulating as well as non-accumulating plants growing on serpentine (S) and non-serpentine (NS) soils, respectively. To test whether the S and NS populations belong to the same or separate closely related species, we analysed genetic variation within and between four S and four NS populations from across the Iberian peninsula. Based on microsatellites, genetic variation was similar in S and NS populations (average Ho=0.48). The populations were significantly differentiated from each other (overall FST=0.23), and the degree of differentiation between S and NS populations was similar to that within these two groups. However, high S versus NS differentiation was observed in DNA polymorphism of two genes putatively involved in adaptation to serpentine environments, IREG1 and NRAMP4, whereas no such differentiation was found in a gene (ASIL1) not expected to play a specific role in ecological adaptation in A. serpyllifolium. These results indicate that S and NS populations belong to the same species and that nickel hyperaccumulation in A. serpyllifolium appears to represent a case of adaptation to growth on serpentine soils. Further functional and evolutionary genetic work in this system has the potential to significantly advance our understanding of the evolution of metal hyperaccumulation in plants.


Assuntos
Adaptação Fisiológica/genética , Brassicaceae/genética , Evolução Molecular , Níquel/metabolismo , Alcaloides de Triptamina e Secologanina/química , Solo/química , Brassicaceae/metabolismo , Genes de Plantas , Variação Genética , Genética Populacional , Repetições de Microssatélites , Portugal , Análise de Sequência de DNA , Espanha
11.
Artigo em Inglês | MEDLINE | ID: mdl-26947583

RESUMO

People with head and neck cancer (HNC) experience elevated symptom toxicity and co-morbidity as a result of treatment, which is associated with poorer psychosocial and quality-of-life (QoL) outcomes. This Phase I study examined whether an individualised mindfulness-based stress reduction (IMBSR) programme could be successfully used with HNC patients undergoing curative treatment. Primary aims were to explore feasibility, compliance, acceptability and fidelity. Secondary aims were to determine whether (1) participation in the intervention was associated with changes in post-intervention mindfulness and (2) post-intervention mindfulness was associated with post-intervention distress and QoL. Nineteen HNC patients participated in a seven-session IMBSR programme with pre- and post-test outcome measures of psychological distress, depression, anxiety and QoL. Primary aims were assessed by therapists or participants. Mindfulness, distress and QoL were assessed using self-report questionnaires at pre- and post-intervention. Longer time spent meditating daily was associated with higher post-intervention mindfulness. After controlling for pre-intervention mindfulness, there was an association between higher post-intervention mindfulness and lower psychological distress and higher total, social and emotional QoL. This study offers important preliminary evidence than an IMBSR intervention can be administered to HNC patients during active cancer treatment. A randomised controlled trial is warranted to confirm these findings.


Assuntos
Ansiedade/terapia , Carcinoma de Células Escamosas/radioterapia , Depressão/terapia , Neoplasias de Cabeça e Pescoço/radioterapia , Atenção Plena/métodos , Estresse Psicológico/terapia , Adulto , Idoso , Ansiedade/psicologia , Austrália , Carcinoma de Células Escamosas/psicologia , Depressão/psicologia , Feminino , Neoplasias de Cabeça e Pescoço/psicologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Qualidade de Vida/psicologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Estresse Psicológico/psicologia , Inquéritos e Questionários , Adulto Jovem
12.
BMC Health Serv Res ; 16(1): 677, 2016 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-27899106

RESUMO

BACKGROUND: Increasing numbers of people with HIV are living into older age and experiencing comorbidities. The development of new models of care to meet the needs of this population is now a priority. It is important that the views and preferences of patients inform the development of services in order to maintain high levels of patient satisfaction and engagement. The aim of this systematic review was to determine which aspects of healthcare are particularly valued by people living with HIV. METHODS: We searched electronic databases and reference lists of relevant articles. The search strategy was developed to identify articles reporting on HIV positive patients' perceptions, evaluations or experiences of healthcare services and factors associated with satisfaction with care. Peer-reviewed papers and conference abstracts were included if the study reported on aspects of health care that were valued by people living with HIV, data were collected during the era of combination therapy (from 1996 onwards), and the paper was published in English. A thematic approach to data synthesis was used. RESULTS: Twenty-three studies met the inclusion criteria. Studies used both qualitative and quantitative methods. Six studies specifically reported on relative importance to patients of different aspects of care. The valued aspects of care identified were grouped into seven themes. These highlighted the importance to patients of: a good health care professional-patient relationship, HIV specialist knowledge, continuity of care, ease of access to services, access to high quality information and support, effective co-ordination between HIV specialists and other healthcare professionals, and involvement in decisions about treatment and care. We were unable to determine the relative importance to patients of different aspects of care because of methodological differences between the studies. CONCLUSIONS: This review identified several attributes of healthcare that are valued by people living with HIV, many of which would be relevant to any future reconfiguration of services to meet the needs of an ageing population. Further research is required to determine the relative importance to patients of different aspects of care.


Assuntos
Atenção à Saúde , Infecções por HIV/terapia , Preferência do Paciente , Países Desenvolvidos , Serviços de Saúde , Humanos , Relações Profissional-Paciente
13.
J Antimicrob Chemother ; 70(4): 1008-15, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25558071

RESUMO

OBJECTIVES: There are limited data on Enterobacter cloacae outbreaks and fewer describing these in association with NDM-1. With whole-genome sequencing, we tested the hypothesis that a cluster of 16 E. cloacae bacteraemia cases in a Nepali neonatal unit represented a single clonal outbreak, using a wider set of epidemiologically unrelated clinical E. cloacae isolates for comparison. METHODS: Forty-three isolates were analysed, including 23 E. cloacae and 3 Citrobacter sp. isolates obtained from blood cultures from 16 neonates over a 3 month period. These were compared with two contemporaneous community-associated drug-resistant isolates from adults, a unit soap dispenser isolate and a set of historical invasive isolates (n=14) from the same geographical locality. RESULTS: There were two clear neonatal outbreaks and one isolated case in the unit. One outbreak was associated with an NDM-1 plasmid also identified in a historical community-associated strain. The smaller, second outbreak was likely associated with a contaminated soap dispenser. The two community-acquired adult cases and three sets of historical hospital-associated neonatal isolates represented four additional genetic clusters. CONCLUSIONS: E. cloacae infections in this context represent several different transmission networks, operating at the community/hospital and host strain/plasmid levels. Wide sampling frames and high-resolution typing methods are needed to describe the complex molecular epidemiology of E. cloacae outbreaks, which is not appropriately reflected by routine susceptibility phenotypes. Soap dispensers may represent a reservoir for E. cloacae and bacterial strains and plasmids may persist in hospitals and in the community for long periods, sporadically being involved in outbreaks of disease.


Assuntos
Bacteriemia/epidemiologia , Surtos de Doenças , Enterobacter cloacae/isolamento & purificação , Infecções por Enterobacteriaceae/epidemiologia , Adulto , Bacteriemia/microbiologia , Bacteriemia/transmissão , Sangue/microbiologia , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , Transmissão de Doença Infecciosa , Enterobacter cloacae/classificação , Enterobacter cloacae/genética , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/transmissão , Microbiologia Ambiental , Genoma Bacteriano , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Epidemiologia Molecular , Dados de Sequência Molecular , Nepal/epidemiologia , Estudos Retrospectivos
14.
Ambix ; 62(1): 50-71, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26173342

RESUMO

This paper is an attempt to document the early history of the quantitative chemical analysis of ceramic materials in Europe, with a specific interest in the analysis of archaeological ceramics. This inevitably leads to a study of the attempts made in Europe to imitate the miraculous material--porcelain--imported from China from the fourteenth century onwards. It is clear that before the end of the eighteenth century progress was made in this endeavor by systematic but essentially trial-and-error firing of various raw materials, culminating in the successful production of European porcelain by Böttger and von Tschirnhaus in 1709. Shortly after this, letters describing the Chinese manufacture of porcelain, and, more importantly, samples of raw and fired material, began to arrive in Europe from French Jesuit missionaries, which were subjected to intense study. Following the perfection of gravimetric methods of chemical analysis in the late eighteenth century, these Chinese samples, and samples of porcelain from various European factories, were regularly analysed, particularly by Brongniart at Sèvres. Similar work was carried out on English porcelain by Simeon Shaw and Sir Arthur Church. The origins of the chemical analysis of archaeological ceramics are still somewhat obscure, but must date to the late eighteenth or early nineteenth centuries, by the likes of Vauquelin and Chaptal.


Assuntos
Cerâmica/história , Cerâmica/química , China , História do Século XVIII
15.
Clin Infect Dis ; 58(7): 949-59, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24403544

RESUMO

BACKGROUND: Protection against Haemophilus influenzae type b (Hib), a rapidly invading encapsulated bacteria, is dependent on maintenance of an adequate level of serum antibody through early childhood. In many countries, Hib vaccine booster doses have been implemented after infant immunization to sustain immunity. We investigated the long-term persistence of antibody and immunological memory in primary-school children following infant (with or without booster) Hib vaccination. METHODS: Anti-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) concentration and the frequency of circulating Hib-specific memory B cells were measured before a booster of a Hib-serogroup C meningococcal (MenC) conjugate vaccine and again 1 week, 1 month, and 1 year after the booster in 250 healthy children aged 6-12 years in an open-label phase 4 clinical study. RESULTS: Six to 12 years following infant priming with 3 doses of Hib conjugate vaccine, anti-PRP IgG geometric mean concentrations were 3.11 µg/mL and 0.71 µg/mL and proportions with anti-PRP IgG ≥1.0 µg/mL were 79% and 43% in children who had or had not, respectively, received a fourth Hib conjugate vaccine dose (mean age, 3.9 years). Higher baseline and post-Hib-MenC booster responses (anti-PRP IgG and memory B cells) were found in younger children and in those who had received a fourth Hib dose. CONCLUSIONS: Sustained Hib conjugate vaccine-induced immunity in children is dependent on time since infant priming and receipt of a booster. Understanding the relationship between humoral and cellular immunity following immunization with conjugate vaccines may direct vaccine design and boosting strategies to sustain individual and population immunity against encapsulated bacteria in early childhood. Clinical Trials Registration ISRCTN728588998.


Assuntos
Linfócitos B/imunologia , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/uso terapêutico , Imunização Secundária , Memória Imunológica , Criança , Feminino , Infecções por Haemophilus/imunologia , Humanos , Imunoglobulina G/sangue , Masculino , Fatores de Tempo
16.
Antimicrob Agents Chemother ; 58(12): 7347-57, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25267672

RESUMO

NDM-producing Klebsiella pneumoniae strains represent major clinical and infection control challenges, particularly in resource-limited settings with high rates of antimicrobial resistance. Determining whether transmission occurs at a gene, plasmid, or bacterial strain level and within hospital and/or the community has implications for monitoring and controlling spread. Whole-genome sequencing (WGS) is the highest-resolution typing method available for transmission epidemiology. We sequenced carbapenem-resistant K. pneumoniae isolates from 26 individuals involved in several infection case clusters in a Nepali neonatal unit and 68 other clinical Gram-negative isolates from a similar time frame, using Illumina and PacBio technologies. Within-outbreak chromosomal and closed-plasmid structures were generated and used as data set-specific references. Three temporally separated case clusters were caused by a single NDM K. pneumoniae strain with a conserved set of four plasmids, one being a 304,526-bp plasmid carrying bla(NDM-1). The plasmids contained a large number of antimicrobial/heavy metal resistance and plasmid maintenance genes, which may have explained their persistence. No obvious environmental/human reservoir was found. There was no evidence of transmission of outbreak plasmids to other Gram-negative clinical isolates, although bla(NDM) variants were present in other isolates in different genetic contexts. WGS can effectively define complex antimicrobial resistance epidemiology. Wider sampling frames are required to contextualize outbreaks. Infection control may be effective in terminating outbreaks caused by particular strains, even in areas with widespread resistance, although this study could not demonstrate evidence supporting specific interventions. Larger, detailed studies are needed to characterize resistance genes, vectors, and host strains involved in disease, to enable effective intervention.


Assuntos
Cromossomos Bacterianos/química , Infecção Hospitalar/epidemiologia , Doenças Endêmicas , Genoma Bacteriano , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/genética , beta-Lactamases/genética , Antibacterianos/uso terapêutico , Mapeamento Cromossômico , Cromossomos Bacterianos/metabolismo , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana , Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Hospitais , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/isolamento & purificação , Nepal/epidemiologia , Plasmídeos/química , Plasmídeos/metabolismo , beta-Lactamases/metabolismo
17.
J Anat ; 224(6): 615-23, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24635640

RESUMO

The proportion of total limb length taken up by the individual skeletal elements (limb proportionality), varies widely between species. These diverse skeletal forms have evolved to allow for a range of limb uses and they first emerge as the embryo develops, to achieve the characteristic skeletal architecture of each species. During this time, the developing skeleton experiences mechanical loading as a result of embryonic muscle contraction. The possibility that adaptation to such mechanical input may allow embryos to coordinate the appearance of skeletal design with their expanding range of movements has so far received little attention. This is surprising, given the critical role exerted by embryo movement in normal skeletal development; stage-specific in ovo immobilisation of embryonic chicks results in joint contractures and a reduction in longitudinal bone growth in the limbs. Epigenetic mechanisms allow for selective activation of genes in response to environmental signals, resulting in the production of phenotypic complexity in morphogenesis; mechanical loading of bone during movement appears to be one such signal. It may be that 'mechanosensitive' genes under regulation of mechanical input adjust proportionality along the bone's proximo-distal axis, introducing a level of phenotypic plasticity. If this hypothesis is upheld, species with more elongated distal limb elements will have a greater dependence on mechanical input for the differences in their growth, and mechanosensitive bone growth in the embryo may have evolved as an additional source of phenotypic diversity during skeletal development.


Assuntos
Fenômenos Biomecânicos/fisiologia , Desenvolvimento Ósseo/fisiologia , Extremidades/embriologia , Movimento/fisiologia , Organogênese/fisiologia , Adaptação Fisiológica , Animais , Embrião de Mamíferos , Humanos , Especificidade da Espécie
18.
Phys Chem Chem Phys ; 16(36): 19446-52, 2014 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-25103112

RESUMO

We doped graphene in situ during synthesis from methane and ammonia on copper in a low-pressure chemical vapour deposition system, and investigated the effect of the synthesis temperature and ammonia concentration on the growth. Raman and X-ray photoelectron spectroscopy was used to investigate the quality and nitrogen content of the graphene and demonstrated that decreasing the synthesis temperature and increasing the ammonia flow rate results in an increase in the concentration of nitrogen dopants up to ca. 2.1% overall. However, concurrent scanning electron microscopy studies demonstrate that decreasing both the growth temperature from 1000 to 900 °C and increasing the N/C precursor ratio from 1/50 to 1/10 significantly decreased the growth rate by a factor of six overall. Using scanning tunnelling microscopy we show that the nitrogen was incorporated mainly in substitutional configuration, while current imaging tunnelling spectroscopy showed that the effect of the nitrogen on the density of states was visible only over a few atom distances.

19.
Public Health ; 128(9): 771-6, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25192883

RESUMO

OBJECTIVES: Climate change has the potential to threaten human health and the environment. Managers in healthcare systems face significant challenges to balance carbon mitigation targets with operational decisions about patient care. Critical care units are major users of energy and hence more evidence is needed on their carbon footprint. STUDY DESIGN: The authors explore a methodology which estimates electricity use and associated carbon emissions within a Critical Care Unit (CCU). METHODS: A bottom-up model was developed and calibrated which predicted the electricity consumed and carbon emissions within a CCU based on the type of patients treated and working practices in a case study in Cornwall, UK. RESULTS: The model developed was able to predict the electricity consumed within CCU with an error of 1% when measured against actual meter readings. Just under half the electricity within CCU was used for delivering care to patients and monitoring their condition. CONCLUSIONS: A model was developed which accurately predicted the electricity consumed within a CCU based on patient types, medical devices used and working practice. The model could be adapted to enable it to be used within hospitals as part of their planning to meet carbon reduction targets.


Assuntos
Pegada de Carbono , Cuidados Críticos , Carbono/efeitos adversos , Mudança Climática , Eletricidade , Humanos , Unidades de Terapia Intensiva , Modelos Teóricos , Reino Unido
20.
Public Health ; 128(10): 920-4, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25304168

RESUMO

OBJECTIVES: Health services must provide safe, affordable clinical care whilst meeting efficiency, environmental and social targets. These targets include achieving reduced greenhouse gas emissions. A care pathway approach based on a decision-support tool can simultaneously reconfigure health services, improve productivity and reduce carbon emissions. STUDY DESIGN: Probabilistic modelling using secondary data analysis. METHODS: Estimates of carbon emitted by a health service drew on a previous carbon accounting study which integrated bottom-up assessment of carbon emissions with top-down analysis of indirect emissions by Duane et al. (2012).(1) Using human resource information, estimates were applied in a decision-support model to measure the carbon footprint and service provision of theoretical scenarios. Using this model, sites with less than 60% utilisation were theoretically reconfigured to reduce carbon emissions and improve service provision. RESULTS: Clinic utilisation rates improved from 50% to 78%. Human resource savings were identified which could be re-directed towards improving patient care. Patient travel for health care was halved resulting in significant savings in carbon emissions. CONCLUSIONS: The proposed model is an effective health care service analysis tool, ensuring optimal utilisation of health care sites and human resources with the lowest carbon footprint.


Assuntos
Pegada de Carbono , Redução de Custos , Atenção à Saúde/economia , Planejamento em Saúde/organização & administração , Preferência do Paciente , Humanos , Modelos Teóricos , Reino Unido
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