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1.
Appetite ; 165: 105283, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33991644

RESUMO

People who do not eat enough fruit and vegetables (F&V) have incremental health risks. Most Europeans do not comply with health recommendations relating to F&V consumption and this is especially true for those with lower-level education, which reinforces structural inequalities in health and wellbeing among Europeans. This study investigated the role of key behavioural triggers - capabilities, opportunities and motivation (in the COM-B model) - as pathways for educational differentials in F&V intake in Europe. A cross-sectional survey-based study was conducted in five European countries differing widely in their consumption habits, wealth, and climatic conditions. A structural equation model was designed to study how capabilities (diet perceived knowledge, health purchase criteria), opportunities (financial availability, social norms), and motivations (health value, habits strength) affect educational inequalities in the intake of F&V (5 portions a day) as mediators. Multi-group comparisons assessed country differences. People with higher levels of education were more likely to eat the recommended diet, i.e., at least 5 portions of F&V a day. Countries in the sample vary significantly in the percentage of people complying with the recommendation, but not significantly in terms of relative education differentials. The educational gap in the intake of F&V is mainly explained by education differentials in financial availability, diet knowledge, and habits in inserting F&V in main meals. Policies targeting dietary inequalities should address behavioural triggers affecting dietary intake, for example by subsidising F&V, developing targeted dietary awareness campaigns, or by intervening in mass catering contexts to facilitate the implementation of healthy habits.


Assuntos
Motivação , Verduras , Estudos Transversais , Dieta , Europa (Continente) , Frutas , Humanos
2.
Orbit ; 38(1): 67-71, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30040513

RESUMO

AIM: The aim of this study is to report a retrospective case series on orbital infantile haemangiomas (OIH). Radiological features and treatment with oral propranolol (OP) are illustrated along with an updated literature review. METHODS: A retrospective chart review of six children, diagnosed with OIH from November 2015 to October 2016, was carried out. Only children with deep documented orbital involvement were included. All patients underwent magnetic resonance imaging (MRI) under general anaesthesia. OP was administered to the infants according to the Nottingham Children's Hospital guideline. As per the guideline, a preliminary paediatric assessment was performed and a 1 mg/kg test dose was administered, followed by definitive treatment at a dosage of 2 mg/kg in three divided doses. RESULTS: Average age at presentation was within the first 3 weeks of life. T1 hypointensity, T2 hyperintensity, avid enhancement with contrast, and the presence of flow-voids appear a fixed pattern of OIH on MRI. Response to treatment was noticed within 4 weeks in all children, and two of them (33.3%) responded within the first 7 days. In two children (33.3%), the haemangioma became clinically undetectable by the seventh month of treatment, while the other four (66.6%) experienced an almost complete regression of the OIH by the last follow-up. No complications were found. CONCLUSIONS: Our series strengthens the understanding that MRI is the preferred imaging modality in the investigation of OIH, showing vascular features, detailed orbital extension, and possible associated malformations. OP is the treatment of choice for OIH, and our study confirms its safety and effectiveness.


Assuntos
Hemangioma Capilar/diagnóstico por imagem , Imageamento por Ressonância Magnética , Neoplasias Orbitárias/diagnóstico por imagem , Propranolol/uso terapêutico , Vasodilatadores/uso terapêutico , Feminino , Hemangioma Capilar/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias Orbitárias/tratamento farmacológico , Estudos Retrospectivos
3.
Clin Immunol ; 175: 1-9, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27856306

RESUMO

Peripheral monocytes from patients with common variable immunodeficiency (CVID) had on average a 2 fold greater tendency to form giant cells in medium without additional cytokines. Giant cell formation was faster and 3 to 5 fold higher in most CVID cells compared to normal. Addition of IL4, GMCSF, IFNγ, TNFa and both T cell and monocyte conditioned media promoted monocyte fusion of some CVID individuals over 5 fold the normal average level, with combinations of cytokines and monokines acting synergistically. The reduction of normal giant cell formation by anti-IFNγ antibody and a greater tendency of CVID cells to fuse in immunoglobulin conditioned media suggests that standard IVIg treatment contributes to granuloma formation. CVID and normal giant cells expressed similar levels of phenotypic molecules and had similar phagocytic activity. Monocytes from many CVID patients have an elevated tendency to fuse which may explain the high incidence of granulomatous complications in CVID.


Assuntos
Imunodeficiência de Variável Comum/imunologia , Células Gigantes/imunologia , Granuloma/imunologia , Doença Granulomatosa Crônica/imunologia , Adulto , Idoso , Feminino , Humanos , Interferon gama/imunologia , Interleucina-4/imunologia , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/imunologia
4.
Proc Natl Acad Sci U S A ; 111(15): E1538-47, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24706810

RESUMO

Studies of replicative and chronological lifespan in Saccharomyces cerevisiae have advanced understanding of longevity in all eukaryotes. Chronological lifespan in this species is defined as the age-dependent viability of nondividing cells. To date this parameter has only been estimated under calorie restriction, mimicked by starvation. Because postmitotic cells in higher eukaryotes often do not starve, we developed a model yeast system to study cells as they age in the absence of calorie restriction. Yeast cells were encapsulated in a matrix consisting of calcium alginate to form ∼3 mm beads that were packed into bioreactors and fed ad libitum. Under these conditions cells ceased to divide, became heat shock and zymolyase resistant, yet retained high fermentative capacity. Over the course of 17 d, immobilized yeast cells maintained >95% viability, whereas the viability of starving, freely suspended (planktonic) cells decreased to <10%. Immobilized cells exhibited a stable pattern of gene expression that differed markedly from growing or starving planktonic cells, highly expressing genes in glycolysis, cell wall remodeling, and stress resistance, but decreasing transcription of genes in the tricarboxylic acid cycle, and genes that regulate the cell cycle, including master cyclins CDC28 and CLN1. Stress resistance transcription factor MSN4 and its upstream effector RIM15 are conspicuously up-regulated in the immobilized state, and an immobilized rim15 knockout strain fails to exhibit the long-lived, growth-arrested phenotype, suggesting that altered regulation of the Rim15-mediated nutrient-sensing pathway plays an important role in extending yeast chronological lifespan under calorie-unrestricted conditions.


Assuntos
Regulação Fúngica da Expressão Gênica/fisiologia , Longevidade/fisiologia , Modelos Biológicos , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/fisiologia , Alginatos , Pontos de Checagem do Ciclo Celular/fisiologia , Células Imobilizadas/metabolismo , Células Imobilizadas/fisiologia , Citometria de Fluxo , Ácido Glucurônico , Ácidos Hexurônicos , Análise em Microsséries , Reprodução/fisiologia
5.
Ear Hear ; 37(3): e202-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26760200

RESUMO

OBJECTIVES: To estimate the annual cost of Ménière's disease and the cost per person in the UK population and to investigate the direct and indirect costs of the condition. DESIGN: The authors utilized a multidata approach to provide the first estimate of the cost of Ménière's. Data from the UK Biobank (a study of 500,000 individuals collected between 2007 and 2012), the Hospital Episode Statistics (data on all hospital admissions in England from 2008 to 2012) and the UK Ménière's Society (2014) were used to estimate the cost of Ménière's. Cases were self-reported in the UK Biobank and UK Ménière's Society, within the Hospital Episode Statistics cases were clinician diagnosed. The authors estimated the direct and indirect costs of the condition, using count data to represent numbers of individuals reporting specific treatments, operations etc. and basic statistical analyses (χ tests, linear and logistic regression) to compare cases and controls in the UK Biobank. RESULTS: Ménière's was estimated to cost between £541.30 million and £608.70 million annually (equivalent to US $829.9 to $934.2 million), equating to £3,341 to £3,757 ($5112 to $5748) per person per annum. The indirect costs were substantial, with loss of earnings contributing to over £400 million per annum. CONCLUSIONS: For the first time, the authors were able to estimate the economic burden of Ménière's disease. In the UK, the annual cost of this condition is substantial. Further research is required to develop cost-effective treatments and management strategies for Ménière's to reduce the economic burden of the disease. These findings should be interpreted with caution due to the uncertainties inherent in the analysis.


Assuntos
Eficiência , Custos de Cuidados de Saúde , Doença de Meniere/economia , Previdência Social/economia , Humanos , Modelos Lineares , Modelos Logísticos , Doença de Meniere/terapia , Desemprego , Reino Unido , Trabalho
6.
Proc Natl Acad Sci U S A ; 110(33): 13322-7, 2013 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-23898165

RESUMO

Examination of three frozen bodies, a 13-y-old girl and a girl and boy aged 4 to 5 y, separately entombed near the Andean summit of Volcán Llullaillaco, Argentina, sheds new light on human sacrifice as a central part of the Imperial Inca capacocha rite, described by chroniclers writing after the Spanish conquest. The high-resolution diachronic data presented here, obtained directly from scalp hair, implies escalating coca and alcohol ingestion in the lead-up to death. These data, combined with archaeological and radiological evidence, deepen our understanding of the circumstances and context of final placement on the mountain top. We argue that the individuals were treated differently according to their age, status, and ritual role. Finally, we relate our findings to questions of consent, coercion, and/or compliance, and the controversial issues of ideological justification and strategies of social control and political legitimation pursued by the expansionist Inca state before European contact.


Assuntos
Sepultamento/história , Comportamento Ritualístico , Múmias/diagnóstico por imagem , Adolescente , Fatores Etários , Arqueologia , Argentina , Pré-Escolar , Cromatografia Líquida , Coca/metabolismo , Etanol/análise , Feminino , Cabelo/química , História Antiga , Humanos , Indígenas Sul-Americanos , Masculino , Múmias/história , Espectrometria de Massas em Tandem , Tomografia Computadorizada por Raios X
7.
Lasers Med Sci ; 30(5): 1619-22, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24162308

RESUMO

Measurements of the electric and magnetic field strengths surrounding six laser systems and one intense pulsed light system were carried out. The results were compared to exposure limits published by cardiac device manufacturers to assess the risk of electromagnetic interference to implantable cardiac devices such as pacemakers or implantable cardioverter defibrillators. The majority of lasers assessed in this study were found to produce electric and magnetic field strengths below the published exposure limits for cardiac devices. However, the low-frequency electric field and static magnetic field of both the CO2 laser and the ruby laser were found to exceed these limits. Ensuring that a small separation is maintained at all times between the laser unit and any patient with a pacemaker or implantable cardioverter defibrillator appears to be a sensible expedient in avoiding overexposure of an implantable cardiac device to electromagnetic interference. Due to the single-shot fast discharge nature of the intense pulsed light system, changes in electromagnetic field strength were too fast for some of the measuring equipment used in this study to register accurate readings during operation.


Assuntos
Desfibriladores Implantáveis , Lasers de Gás , Lasers de Estado Sólido , Marca-Passo Artificial , Campos Eletromagnéticos , Humanos
8.
J Math Biol ; 69(1): 183-211, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23739839

RESUMO

Over the years numerous models of S I S (susceptible --> infected --> susceptible) disease dynamics unfolding on networks have been proposed. Here, we discuss the links between many of these models and how they can be viewed as more general motif-based models. We illustrate how the different models can be derived from one another and, where this is not possible, discuss extensions to established models that enables this derivation. We also derive a general result for the exact differential equations for the expected number of an arbitrary motif directly from the Kolmogorov/master equations and conclude with a comparison of the performance of the different closed systems of equations on networks of varying structure.


Assuntos
Doenças Transmissíveis/transmissão , Epidemias , Modelos Biológicos , Doenças Transmissíveis/epidemiologia , Simulação por Computador , Humanos
9.
Insect Sci ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605428

RESUMO

Leaf cutting ants of the genus Atta cultivate fungal gardens, carefully modifying environmental conditions to maintain optimal temperature for fungal growth. Antennal nerves from Atta are highly temperature sensitive, but the underlying molecular sensor is unknown. Here, we utilize Atta texana (Texas leaf cutter ant) to investigate the molecular basis of ant temperature sensation and how it might have evolved as the range expanded northeast across Texas from ancestral populations in Mexico. We focus on transient receptor potential (TRP) channel genes, the best characterized temperature sensor proteins in animals. Atta texana antennae express 6 of 13 Hymenopteran TRP channel genes and sequences are under a mix of relaxed and intensified selection. In a behavioral assay, we find A. texana workers prefer 24 °C (range 21-26 °C) for fungal growth. There was no evidence of regulatory evolution across a temperature transect in Texas, but instead Hymenoptera-specific TRPA (HsTRPA) expression highly correlated with ambient temperature. When expressed in vitro, HsTRPA from A. texana is temperature activated with Q10 values exceeding 100 on initial exposure to temperatures above 33 °C. Surprisingly, HsTRPA also appears to be activated by cooling, and therefore to our knowledge, the first non-TRPA1 ortholog to be described with dual heat/cold activation and the first in any invertebrate.

10.
Environ Sci Technol ; 47(2): 678-86, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23244244

RESUMO

Increasing greenhouse gas emissions threaten human health and the environment. In response, healthcare managers face significant challenges in balancing operational decisions about patient care with carbon mitigation targets. We explore a bottom-up modeling framework to aid in the decision-making for both carbon and cost in healthcare, using data from a case study in Cornwall, UK. A model was built and run for secondary healthcare, specifically outpatient clinics, theater lists, beds, and diagnostic facilities. Five scenarios were tested: business-as-usual; service expansion; site closure; water temperature reduction; and theater optimization. The estimated emissions from secondary healthcare in Cornwall ran to 5787 T CO(2)eq with patient travel adding 2215 T CO(2)eq. Closing selected sites would have reduced this by 4% (261 T CO(2)eq), a reduction less than the resulting increases in patient transport emissions. Reducing hot water temperatures by 5 °C and improving theater usage would lower the footprint by 0.7% (44 T CO(2)eq) and 0.08% (5 T CO(2)eq), respectively. We consider bottom-up models important tools in the process of estimating and modeling the carbon footprint of healthcare. For the carbon reduction targets of the healthcare sector to be met, the use of these bottom-up models in decision making and forward planning is pivotal.


Assuntos
Pegada de Carbono/economia , Atenção à Saúde/economia , Atenção à Saúde/organização & administração , Efeito Estufa/prevenção & controle , Formulação de Políticas , Humanos , Modelos Teóricos , Reino Unido
11.
Artigo em Inglês | MEDLINE | ID: mdl-36673833

RESUMO

(1) Background: Poor air quality affects health and causes premature death and disease. Outdoor air quality has received significant attention, but there has been less focus on indoor air quality and what drives levels of diverse pollutants in the home, such as particulate matter, and the impact this has on health; (2) Methods: This study conducts analysis of cross-sectional data from the Smartline project. Analyses of data from 279 social housing properties with indoor sensor data were used to assess multiple factors that could impact levels of particulate matter. T-Tests and Anova tests were used to explore associations between elevated PM2.5 and building, household and smoking and vaping characteristics. Binary logistic regression was used to test the association between elevated particulate matter and self-reported health; (3) Results: Of the multiple potential drivers of the particulate matter investigated, smoking and vaping were significantly associated with mean PM2.5. Following multivariate analysis, only smoking remained significantly associated with higher mean concentrations. Properties in which <15 cigarettes/day were smoked were predicted to have PM2.5 concentrations 9.06 µg/m3 higher (95% CI 6.4, 12.82, p ≤ 0.001) than those in which residents were non-smokers and 11.82 µg/m3 higher (95% CI 7.67, 18.19, p ≤ 0.001) where >15 cigarettes were smoked; (4) Conclusions: A total of 25% of social housing properties in this study experienced levels of indoor PM greater than WHO guideline levels for ambient air pollution. Although there are many factors that impact air quality, in this study the main driver was smoking. This highlights the importance of targeting smoking in indoor environments in future smoking cessation and control policy and practice and of understanding how pollutants interact in the home environment. There is also a need for further research into the impact on indoor air quality of vaping, particularly due to the rise in use and uncertainty of its long-term impact.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluição do Ar , Humanos , Poluentes Atmosféricos/análise , Estudos Transversais , Monitoramento Ambiental , Poluição do Ar/análise , Material Particulado/análise , Poluição do Ar em Ambientes Fechados/análise
12.
J Environ Qual ; 41(2): 454-68, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22370409

RESUMO

Surface mining is a common method for extracting coal in the coal fields of eastern Kentucky. Using the Forestry Reclamation Approach (FRA), which emphasizes the use of minimally compacted or loose-dumped spoil as a growth medium for trees, reclamation practitioners are successfully reestablishing forests. Yet, questions remain regarding the effects FRA has on the quality of waters discharged to receiving streams. To examine the effect of FRA on water quality, this study compared waters that were discharged from three types of spoils: predominantly brown, weathered sandstone (BROWN); predominantly gray, unweathered sandstone (GRAY); and an equal mixture of both aforementioned sandstones and shale (MIXED). The water quality parameters pH, EC, Ca, K, Mg, Na, NO-N, NH-N, SO, Cl, TC, suspended sediment concentration (SSC), settleable solids (SS), and turbidity were monitored over a 2-yr period on six 0.4-ha plots (two replications per spoil type). Generally, levels of Cl, SO, Ca, NO-N, NH-N, SS, SSC, and turbidity decreased over time. The pH for all spoils increased from about 7.5 to 8.5. The EC remained relatively level in the BROWN spoil, whereas the GRAY and MIXED spoils had downward trajectories that were approaching 500 µS cm. The value of 500 µS cm has been reported as the apparent threshold at which certain taxa such as Ephemeroptera (e.g., Mayfly) recolonize disturbed headwater streams of eastern Kentucky and adjacent coal-producing Appalachian states.


Assuntos
Resíduos Industriais/análise , Mineração , Árvores , Qualidade da Água , Condutividade Elétrica , Concentração de Íons de Hidrogênio , Resíduos Industriais/efeitos adversos , Kentucky , Árvores/efeitos dos fármacos , Árvores/crescimento & desenvolvimento , Água/química
13.
Pract Midwife ; 15(6): 14-7, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22860353

RESUMO

Jaundice is common in neonates and is often the reason for a parent to consult a community midwife or health visitor. It is known that up to 40 per cent of breastfed infants are jaundiced at 14 days of age and a proportion of these infants are referred to paediatric services for assessment and blood investigations. Most often the investigations reveal a high bilirubin level but otherwise normal liver function results, leading to a diagnosis of breastfeeding jaundice, with no treatment required other than reassurance to the parents and monitoring. A recent clinical audit is presented which evaluates current clinical practice and the results reflect breast feeding as the main reason for prolonged jaundice. This is followed by some guidance for the community health practitioners with the aim of reducing referral of otherwise well neonates with jaundice and reducing invasive investigations.


Assuntos
Aleitamento Materno , Cuidado do Lactente/métodos , Icterícia Neonatal/diagnóstico , Icterícia Neonatal/enfermagem , Tocologia/métodos , Bilirrubina/sangue , Doença Crônica , Feminino , Humanos , Recém-Nascido , Masculino , Triagem Neonatal/métodos , Prognóstico
14.
Int J Community Wellbeing ; 5(3): 559-570, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35611238

RESUMO

The mental wellbeing of those living in resource poor and rural localities is a public health priority. Despite evidence of a link between social networks and mental wellbeing, little is known about this relationship in the context of rural and resource poor environments. The current study uses novel social network methodology to investigate the extent to which social network size and composition is related to mental wellbeing in a social housing community in rural England. Data come from 88 individuals living in social housing in Cornwall. These participants are part of a larger study of 329 social housing households surveyed in 2017 and 2018. Mental wellbeing was measured by the Short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS). A series of multivariable linear regression models were used to test associations between social network characteristics and mental wellbeing. Social network size was significantly associated with the SWEMWBS (b = 0.39, p < 0.01), such that individuals with larger networks reported better mental wellbeing, but after controlling for community social cohesion, this effect dissipated. Neither gender composition or talking with network members about health and wellbeing were significantly associated with the SWEMWBS. Findings suggest that both the quantity of social connections and perceptions of community cohesion are moderately associated with mental wellbeing in rural and resource poor localities. As such, efforts to improve mental wellbeing would benefit from targeting multiple aspects of social relationships, rather than focusing solely on increasing the size of individuals' social networks.

15.
ACS Nano ; 16(10): 16713-16723, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36174128

RESUMO

Ordered mesoscale structures in 2D materials induced by small misorientations have allowed for a wide variety of electronic, ferroelectric, and quantum phenomena to be explored. Until now, the only mechanism to induce this periodic ordering was via mechanical rotations between the layers, with the periodicity of the resulting moiré pattern being directly related to twist angle. Here we report a fundamentally distinct mechanism for emergence of mesoscopic periodic patterns in multilayer sulfur-containing metal phosphorus trichalcogenide, MnPS3, induced by the electron beam. The formation under the beam of periodic hexagonal patterns with several characteristic length scales, nucleation and transitions between the phases, and local dynamics are demonstrated. The associated mechanisms are attributed to the relative contraction of the layers caused by beam-induced sulfur vacancy formation with subsequent ordering and lattice parameter change. As a result, the plasmonic response of the system is locally altered, suggesting an element of control over plasmon resonances by electron beam patterning. We pose that harnessing this phenomenon provides both insight into fundamental physics of quantum materials and enables device applications by enabling controlled periodic potentials on the atomic scale.

16.
Wellcome Open Res ; 7: 237, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36865374

RESUMO

Natural environments, such as parks, woodlands and lakes, have positive impacts on health and wellbeing. Urban Green and Blue Spaces (UGBS), and the activities that take place in them, can significantly influence the health outcomes of all communities, and reduce health inequalities. Improving access and quality of UGBS needs understanding of the range of systems (e.g. planning, transport, environment, community) in which UGBS are located. UGBS offers an ideal exemplar for testing systems innovations as it reflects place-based and whole society processes , with potential to reduce non-communicable disease (NCD) risk and associated social inequalities in health. UGBS can impact multiple behavioural and environmental aetiological pathways. However, the systems which desire, design, develop, and deliver UGBS are fragmented and siloed, with ineffective mechanisms for data generation, knowledge exchange and mobilisation. Further, UGBS need to be co-designed with and by those whose health could benefit most from them, so they are appropriate, accessible, valued and used well. This paper describes a major new prevention research programme and partnership, GroundsWell, which aims to transform UGBS-related systems by improving how we plan, design, evaluate and manage UGBS so that it benefits all communities, especially those who are in poorest health. We use a broad definition of health to include physical, mental, social wellbeing and quality of life. Our objectives are to transform systems so that UGBS are planned, developed, implemented, maintained and evaluated with our communities and data systems to enhance health and reduce inequalities. GroundsWell will use interdisciplinary, problem-solving approaches to accelerate and optimise community collaborations among citizens, users, implementers, policymakers and researchers to impact research, policy, practice and active citizenship. GroundsWell will be shaped and developed in three pioneer cities (Belfast, Edinburgh, Liverpool) and their regional contexts, with embedded translational mechanisms to ensure that outputs and impact have UK-wide and international application.

17.
Bioorg Med Chem Lett ; 21(12): 3708-11, 2011 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-21565499

RESUMO

High throughput screening (HTS) of our compound file provided an attractive lead compound with modest P2X(7) receptor antagonist potency and high selectivity against a panel of receptors and channels, but also with high human plasma protein binding and a predicted short half-life in humans. Multi-parameter optimization was used to address the potency, physicochemical and pharmacokinetic properties which led to potent P2X(7)R antagonists with good disposition properties. Compound 33 (CE-224,535) was advanced to clinical studies for the treatment of rheumatoid arthritis.


Assuntos
Benzamidas , Descoberta de Drogas , Antagonistas do Receptor Purinérgico P2 , Receptores Purinérgicos P2X7/metabolismo , Uracila/análogos & derivados , Administração Oral , Animais , Antirreumáticos/síntese química , Antirreumáticos/química , Antirreumáticos/farmacocinética , Antirreumáticos/farmacologia , Benzamidas/síntese química , Benzamidas/química , Benzamidas/farmacocinética , Benzamidas/farmacologia , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Ligação Proteica/efeitos dos fármacos , Antagonistas do Receptor Purinérgico P2/síntese química , Antagonistas do Receptor Purinérgico P2/química , Antagonistas do Receptor Purinérgico P2/farmacocinética , Antagonistas do Receptor Purinérgico P2/farmacologia , Ratos , Relação Estrutura-Atividade , Uracila/síntese química , Uracila/química , Uracila/farmacocinética , Uracila/farmacologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-34202018

RESUMO

In response to the COVID-19 outbreak, the UK Government provided public health advice to stay at home from 16 March 2020, followed by instruction to stay at home (full lockdown) from 24 March 2020. We use data with high temporal resolution from utility sensors installed in 280 homes across social housing in Cornwall, UK, to test for changes in domestic electricity, gas and water usage in response to government guidance. Gas usage increased by 20% following advice to stay at home, the week before full lockdown, although no difference was seen during full lockdown itself. During full lockdown, morning electricity usage shifted to later in the day, decreasing at 6 a.m. and increasing at midday. These changes in energy were echoed in water usage, with a 17% increase and a one-hour delay in peak morning usage. Changes were consistent with people getting up later, spending more time at home and washing more during full lockdown. Evidence for these changes was also observed in later lockdowns, but not between lockdowns. Our findings suggest more compliance with an enforced stay-at-home message than with advice. We discuss implications for socioeconomically disadvantaged households given the indication of inability to achieve increased energy needs during the pandemic.


Assuntos
COVID-19 , Controle de Doenças Transmissíveis , Humanos , SARS-CoV-2 , Reino Unido , Água
19.
JMIR Public Health Surveill ; 7(2): e25037, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591284

RESUMO

BACKGROUND: Personas, based on customer or population data, are widely used to inform design decisions in the commercial sector. The variety of methods available means that personas can be produced from projects of different types and scale. OBJECTIVE: This study aims to experiment with the use of personas that bring together data from a survey, household air measurements and electricity usage sensors, and an interview within a research and innovation project, with the aim of supporting eHealth and eWell-being product, process, and service development through broadening the engagement with and understanding of the data about the local community. METHODS: The project participants were social housing residents (adults only) living in central Cornwall, a rural unitary authority in the United Kingdom. A total of 329 households were recruited between September 2017 and November 2018, with 235 (71.4%) providing complete baseline survey data on demographics, socioeconomic position, household composition, home environment, technology ownership, pet ownership, smoking, social cohesion, volunteering, caring, mental well-being, physical and mental health-related quality of life, and activity. K-prototype cluster analysis was used to identify 8 clusters among the baseline survey responses. The sensor and interview data were subsequently analyzed by cluster and the insights from all 3 data sources were brought together to produce the personas, known as the Smartline Archetypes. RESULTS: The Smartline Archetypes proved to be an engaging way of presenting data, accessible to a broader group of stakeholders than those who accessed the raw anonymized data, thereby providing a vehicle for greater research engagement, innovation, and impact. CONCLUSIONS: Through the adoption of a tool widely used in practice, research projects could generate greater policy and practical impact, while also becoming more transparent and open to the public.


Assuntos
Participação da Comunidade/métodos , Difusão de Inovações , Habitação/estatística & dados numéricos , Telemedicina/estatística & dados numéricos , Adulto , Idoso , Telefone Celular , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Rede Social , Inquéritos e Questionários , Reino Unido , Design Centrado no Usuário
20.
Philos Trans R Soc Lond B Biol Sci ; 376(1829): 20200266, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34053271

RESUMO

As several countries gradually release social distancing measures, rapid detection of new localized COVID-19 hotspots and subsequent intervention will be key to avoiding large-scale resurgence of transmission. We introduce ASMODEE (automatic selection of models and outlier detection for epidemics), a new tool for detecting sudden changes in COVID-19 incidence. Our approach relies on automatically selecting the best (fitting or predicting) model from a range of user-defined time series models, excluding the most recent data points, to characterize the main trend in an incidence. We then derive prediction intervals and classify data points outside this interval as outliers, which provides an objective criterion for identifying departures from previous trends. We also provide a method for selecting the optimal breakpoints, used to define how many recent data points are to be excluded from the trend fitting procedure. The analysis of simulated COVID-19 outbreaks suggests ASMODEE compares favourably with a state-of-art outbreak-detection algorithm while being simpler and more flexible. As such, our method could be of wider use for infectious disease surveillance. We illustrate ASMODEE using publicly available data of National Health Service (NHS) Pathways reporting potential COVID-19 cases in England at a fine spatial scale, showing that the method would have enabled the early detection of the flare-ups in Leicester and Blackburn with Darwen, two to three weeks before their respective lockdown. ASMODEE is implemented in the free R package trendbreaker. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.


Assuntos
COVID-19/epidemiologia , Modelos Teóricos , Pandemias , SARS-CoV-2/patogenicidade , Algoritmos , COVID-19/transmissão , COVID-19/virologia , Controle de Doenças Transmissíveis , Inglaterra/epidemiologia , Humanos , Reino Unido/epidemiologia
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