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1.
Nature ; 565(7741): 581-586, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30700868

RESUMO

Focusing laser light onto a very small target can produce the conditions for laboratory-scale nuclear fusion of hydrogen isotopes. The lack of accurate predictive models, which are essential for the design of high-performance laser-fusion experiments, is a major obstacle to achieving thermonuclear ignition. Here we report a statistical approach that was used to design and quantitatively predict the results of implosions of solid deuterium-tritium targets carried out with the 30-kilojoule OMEGA laser system, leading to tripling of the fusion yield to its highest value so far for direct-drive laser fusion. When scaled to the laser energies of the National Ignition Facility (1.9 megajoules), these targets are predicted to produce a fusion energy output of about 500 kilojoules-several times larger than the fusion yields currently achieved at that facility. This approach could guide the exploration of the vast parameter space of thermonuclear ignition conditions and enhance our understanding of laser-fusion physics.

2.
Cleft Palate Craniofac J ; : 10556656231225575, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38408738

RESUMO

OBJECTIVE: To investigate speech development of children aged 5 and 10 years with repaired unilateral cleft lip and palate (UCLP) and identify speech characteristics when speech proficiency is not at 'peer level' at 10 years. Estimate how the number of speech therapy visits are related to speech proficiency at 10 years, and what factors are predictive of whether a child's speech proficiency at 10 years is at 'peer level' or not. DESIGN: Longitudinal complete datasets from the Scandcleft project. PARTICIPANTS: 320 children from nine cleft palate teams in five countries, operated on with one out of four surgical methods. INTERVENTIONS: Secondary velopharyngeal surgery (VP-surgery) and number of speech therapy visits (ST-visits), a proxy for speech intervention. MAIN OUTCOME MEASURES: 'Peer level' of percentage of consonants correct (PCC, > 91%) and the composite score of velopharyngeal competence (VPC-Sum, 0-1). RESULTS: Speech proficiency improved, with only 23% of the participants at 'peer level' at 5 years, compared to 56% at 10 years. A poorer PCC score was the most sensitive marker for the 44% below 'peer level' at 10-year-of-age. The best predictor of 'peer level' speech proficiency at 10 years was speech proficiency at 5 years. A high number of ST-visits received did not improve the probability of achieving 'peer level' speech, and many children seemed to have received excessive amounts of ST-visits without substantial improvement. CONCLUSIONS: It is important to strive for speech at 'peer level' before age 5. Criteria for speech therapy intervention and for methods used needs to be evidence-based.

3.
J Cell Mol Med ; 27(6): 864-878, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36824012

RESUMO

The immunomodulatory characteristics of mesenchymal stromal cells (MSC) confers them with potential therapeutic value in the treatment of inflammatory/immune-mediated conditions. Previous studies have reported only modest beneficial effects in murine models of liver injury. In our study we explored the role of MSC priming to enhance their effectiveness. Herein we demonstrate that stimulation of human MSC with cytokine TGß1 enhances their homing and engraftment to human and murine hepatic sinusoidal endothelium in vivo and in vitro, which was mediated by increased expression of CXCR3. Alongside improved hepatic homing there was also greater reduction in liver inflammation and necrosis, with no adverse effects, in the CCL4 murine model of liver injury treated with primed MSC. Priming of MSCs with TGFß1 is a novel strategy to improve the anti-inflammatory efficacy of MSCs.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Animais , Camundongos , Citocinas/metabolismo , Fígado/metabolismo , Anti-Inflamatórios/metabolismo , Células-Tronco Mesenquimais/metabolismo , Receptores CXCR3/metabolismo
4.
Br J Clin Pharmacol ; 89(2): 672-686, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35986928

RESUMO

AIM: Older adults are particularly affected by medication-related harm (MRH) during transitions of care. There are no clinical tools predicting those at highest risk of MRH post hospital discharge. The PRIME study (prospective study to develop a model to stratify the risk of MRH in hospitalized patients) developed and internally validated a risk-prediction tool (RPT) that provides a percentage score of MRH in adults over 65 in the 8 weeks following hospital discharge. This qualitative study aimed to explore the views of hospital pharmacists around enablers and barriers to clinical implementation of the PRIME-RPT. METHODS: Ten hospital pharmacists: (band 6, n = 3; band 7, n = 2; band 8, n = 5) participated in semistructured interviews at the Royal Sussex County Hospital (Brighton, UK). The pharmacists were presented with five case-vignettes each with a calculated PRIME-RPT score to help guide discussion. Case-vignettes were designed to be representative of common clinical encounters. Data were thematically analysed using a "framework" approach. RESULTS: Seven themes emerged in relation to the PRIME-RPT: (1) providing a medicine-prioritisation aide; (2) acting as a deprescribing alert; (3) facilitating a holistic review of patient medication management; (4) simplifying communication of MRH to patients and the multidisciplinary team; (5) streamlining community follow-up and integration of risk discussion into clinical practice; (6) identifying barriers for the RPTs integration in clinical practice; and (7) acknowledging its limitations. CONCLUSION: Hospital pharmacists found the PRIME-RPT beneficial in identifying older patients at high risk of MRH following hospital discharge, facilitating prioritising interventions to those at highest risk while still acknowledging its limitations.


Assuntos
Alta do Paciente , Farmacêuticos , Humanos , Idoso , Estudos Prospectivos , Pesquisa Qualitativa , Hospitais
5.
Paediatr Respir Rev ; 47: 27-29, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37487798

RESUMO

We present a case of a 10-year-old boy initially diagnosed with CF based on NBS guidelines. However, as CF genetics knowledge has advanced, he has been reclassified as CFSPID based on normal investigations and excellent general clinical status, in line with updated CFSPID guidelines. This case highlights the significance of reviewing CF diagnoses according to the latest understanding of CFTR mutation phenotypes, as well as the patient's clinical status. In order to identify opportunities to save patients from burdensome CF treatment and management, we review current CFSPID guidelines, emphasizing care tailored to each individual case.


Assuntos
Fibrose Cística , Recém-Nascido , Masculino , Humanos , Criança , Fibrose Cística/genética , Desmame , Triagem Neonatal , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fenótipo , Mutação
6.
World J Surg ; 47(12): 3060-3069, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37747549

RESUMO

BACKGROUND: Appendicitis is one of the most common emergency surgical conditions worldwide. Delays in accessing appendectomy can lead to complications. Evidence on these delays in low- and middle-income countries (LMICs) is lacking. The aim of this review was to identify and synthesise the available evidence on delays to accessing appendectomy in LMICs. METHODS: This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews framework. The delays and their interconnectivity in LMICs were synthesised and interpreted using the Three Delays framework. We reviewed Africa Wide EBSCOhost, PubMed-Medline, Scopus, Web of Science, African Journals Online (AJOL), and Bioline databases. RESULTS: Our search identified 21 893 studies, of which 78 were included in the final analysis. All of the studies were quantitative. Fifty per cent of the studies included all three types of delays. Delays in seeking care were influenced by a lack of awareness of appendicitis symptoms, and the use of self and alternative medication, which could be linked to delays in receiving care, and the barrier refusal of medical treatment due to fear. Financial concerns were a barrier observed throughout the care pathway. CONCLUSION: This review highlighted the need for additional studies on delays to accessing appendectomy in additional LMICs. Our review demonstrates that in LMICs, persons seeking appendectomy present late to health-care facilities due to several patient-related factors. After reaching a health-care facility, accessing appendectomy can further be delayed owing to a lack of adequate hospital resources.


Assuntos
Apendicite , Países em Desenvolvimento , Humanos , Apendicectomia , Apendicite/cirurgia , Instalações de Saúde , Hospitais
7.
Community Dent Health ; 40(3): 154-161, 2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37162290

RESUMO

BACKGROUND: There has been a 37% increase in the number of Looked After Children (LAC) in England over the past decade. Although LAC have more health and social problems than their peers, little is known about their dental needs, barriers to dental care, and pathways used to access it. OBJECTIVES: This scoping review assessed the evidence on the dental health needs of LAC in the UK and their different dental care pathways. METHODS: Embase, MedLine(R), Scopus, Web of Science, PubMed and CINAHL, grey literature databases and third-sector organisation websites were searched up to February 2022. Included studies were any study type involving UK resident LAC aged 0-18 with no limits placed on time in care/placement. Thematic analysis identified access barriers and dental care pathways. RESULTS: Twenty-eight articles were included (nine publications, 11 abstracts and 8 grey literature). Oral health surveys, population linkages studies and service evaluations described the poor oral health of LAC and their unmet needs. Barriers included the lack of dental care and irregular attendance; the lack of integrated working between health and social care teams, lack of self-care and oral health promotion, and psychological issues complicating dental treatment. Four dental care pathway models were identified: care navigation, facilitated access, nurse-led triage and referral, and signposting to local dentist with multi-agency information sharing. CONCLUSION: LAC are a vulnerable group with barriers to care suggesting the need for integrated working between health and social care teams, specialist services and an evaluation of pathways to identify best practice.


Assuntos
Procedimentos Clínicos , Saúde Bucal , Humanos , Criança , Promoção da Saúde , Inquéritos de Saúde Bucal , Reino Unido
8.
Int J Lang Commun Disord ; 58(3): 892-909, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36541222

RESUMO

BACKGROUND & AIM: To assess consonant proficiency and velopharyngeal function in 10-year-old children born with unilateral cleft lip and palate (UCLP) within the Scandcleft project. METHODS & PROCEDURES: Three parallel group, randomized, clinical trials were undertaken as an international multicentre study by nine cleft teams in five countries. Three different surgical protocols for primary palate repair (Arm B-Lip and soft palate closure at 3-4 months, hard palate closure at 36 months, Arm C-Lip closure at 3-4 months, hard and soft palate closure at 12 months, and Arm D-Lip closure at 3-4 months combined with a single-layer closure of the hard palate using a vomer flap, soft palate closure at 12 months) were tested against a common procedure (Arm A-Lip and soft palate closure at 3-4 months followed by hard palate closure at 12 months) in the total cohort of 431 children born with a non-syndromic UCLP. Speech audio and video recordings of 399 children were available and perceptually analysed. Percentage of consonants correct (PCC) from a naming test, an overall rating of velopharyngeal competence (VPC) (VPC-Rate), and a composite measure (VPC-Sum) were reported. OUTCOMES & RESULTS: The mean levels of consonant proficiency (PCC score) in the trial arms were 86-92% and between 58% and 83% of the children had VPC (VPC-Sum). Only 50-73% of the participants had a consonant proficiency level with their peers. Girls performed better throughout. Long delay of the hard palate repair (Arm B) indicated lower PCC and simultaneous hard and soft palate closure higher (Arm C). However, the proportion of participants with primary VPC (not including velopharyngeal surgeries) was highest in Arm B (68%) and lowest in Arm C (47%). CONCLUSIONS & IMPLICATIONS: The speech outcome in terms of PCC and VPC was low across the trials. The different protocols had their pros and cons and there is no obvious evidence to recommend any of the protocols as superior. Aspects other than primary surgical method, such as time after velopharyngeal surgery, surgical experience, hearing level, language difficulties and speech therapy, need to be thoroughly reviewed for a better understanding of what has affected speech outcome at 10 years. WHAT THIS PAPER ADDS: What is already known on the subject Speech outcomes at 10 years of age in children treated for UCLP are sparse and contradictory. Previous studies have examined speech outcomes and the relationship with surgical intervention in 5-year-olds. What this study adds to the existing knowledge Speech outcomes based on standardized assessment in a large group of 10-year-old children born with UCLP and surgically treated according to different protocols are presented. While speech therapy had been provided, a large proportion of the children across treatment protocols still needed further speech therapy. What are the potential or actual clinical implications of this work? Aspects other than surgery and speech function might add to the understanding of what affects speech outcome. Effective speech therapy should be available for children in addition to primary surgical repair of the cleft and secondary surgeries if needed.


Assuntos
Fenda Labial , Fissura Palatina , Insuficiência Velofaríngea , Criança , Feminino , Humanos , Pré-Escolar , Fissura Palatina/cirurgia , Fissura Palatina/complicações , Fenda Labial/cirurgia , Fenda Labial/complicações , Fala , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Palato Duro , Insuficiência Velofaríngea/cirurgia , Insuficiência Velofaríngea/complicações
9.
Tech Coloproctol ; 27(11): 979-993, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37632643

RESUMO

PURPOSE: Complete mesocolic excision improves lymphadenectomy for right hemicolectomy and respects the embryological planes. However, its effect on cancer-free and overall survival is questioned. Therefore, we aimed to determine the potential benefits of the technique by performing a systematic review of the literature and meta-analysis of the available evidence. METHODS: Web of Science, PubMed/Medline, and Embase were searched on February 22, 2023. Original studies on short- and long-term oncological outcomes of adult patients undergoing right hemicolectomy with complete mesocolic excision as a treatment for primary colon cancer were considered for inclusion. Outcomes were extracted and pooled using a model with random effects. RESULTS: A total of 586 publications were identified through database searching, and 18 from citation searching. Exclusion of 552 articles left 24 articles for inclusion. Meta-analysis showed that complete mesocolic excision increased the lymph node harvest (5 studies, 1479 patients, MD 9.62, 95% CI 5.83-13.41, p > 0.0001, I2 84%), 5-year overall survival (5 studies, 2381 patients, OR 1.88, 95% CI 1.14-3.09, p = 0.01, I2 66%), 5-year disease-free survival (4 studies, 1376 patients, OR 2.21, 95% CI 1.51-3.23, p < 0.0001, I2 0%) and decreased the incidence of local recurrence (4 studies, 818 patients, OR 0.27, 95% CI 0.09-0.79, p = 0.02, I2 0%) when compared to standard right hemicolectomy. Perioperative morbidity was similar between the techniques (8 studies, 3899 patients, OR 1.04, 95% CI 0.89-1.22, p = 0.97, I2 0%). CONCLUSION: Meta-analysis of observational and randomised studies showed that right hemicolectomy with complete mesocolic excision for primary right colon cancer improves oncologic results without increasing morbidity/mortality. These results need to be confirmed by high-quality evidence and randomised trials in selected patients to assess who may benefit from the procedure.


Assuntos
Neoplasias do Colo , Laparoscopia , Mesocolo , Adulto , Humanos , Neoplasias do Colo/patologia , Excisão de Linfonodo/métodos , Linfonodos/patologia , Intervalo Livre de Doença , Colectomia/métodos , Mesocolo/cirurgia , Mesocolo/patologia , Laparoscopia/métodos , Resultado do Tratamento
10.
Phys Rev Lett ; 128(19): 195002, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35622051

RESUMO

This Letter presents the first observation on how a strong, 500 kG, externally applied B field increases the mode-two asymmetry in shock-heated inertial fusion implosions. Using a direct-drive implosion with polar illumination and imposed field, we observed that magnetization produces a significant increase in the implosion oblateness (a 2.5× larger P2 amplitude in x-ray self-emission images) compared with reference experiments with identical drive but with no field applied. The implosions produce strongly magnetized electrons (ω_{e}τ_{e}≫1) and ions (ω_{i}τ_{i}>1) that, as shown using simulations, restrict the cross field heat flow necessary for lateral distribution of the laser and shock heating from the implosion pole to the waist, causing the enhanced mode-two shape.

11.
Paediatr Respir Rev ; 42: 29-34, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34998674

RESUMO

There is now increased knowledge and experience of newborn screening around the world. There is also a better understanding of CF gene analysis, informed by international databases. This has resulted in a small number of children and adults having their diagnosis of CF reversed. This article illustrates this issue with three cases. It considers how best to tell children and adults with their families, and the reactions that may be encountered. It also discusses practical issues of removing the diagnosis.


Assuntos
Fibrose Cística , Adulto , Criança , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Testes Genéticos , Humanos , Recém-Nascido , Triagem Neonatal/métodos
12.
Paediatr Respir Rev ; 42: 23-28, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34215541

RESUMO

There has been growing interest in telemedicine for cystic fibrosis over recent years based largely on convenience for patients and/or increasing the frequency of surveillance and early detection which, it is assumed, could improve treatment outcomes. During 2020, the covid-19 pandemic catalysed the pace of development of this field, as CF patients were presumed to be at high risk of infection. Most clinics adapted to digital platforms with provision of lung function monitoring and sample collection systems. Here, we present the views of multidisciplinary team members at a large paediatric CF centre on what has worked well and what requires further optimisation in the future. In response to the question posed, 'Do we still need face to face clinics?' our answer is 'Yes, but not every time, and not for everyone'.


Assuntos
Fibrose Cística , Telemedicina , COVID-19 , Criança , Fibrose Cística/diagnóstico , Fibrose Cística/epidemiologia , Fibrose Cística/terapia , Humanos , Pandemias
13.
Age Ageing ; 51(3)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35352796

RESUMO

AIM: Cardiovascular disease (CVD) is common amongst frail older people. The evidence base for CVD commonly excludes older adults with multimorbidity or chronic conditions. Most cardiovascular drugs have the potential to lower blood pressure (BP) and therefore cause medication-related harm (MRH). We aimed to identify key clinical and sociodemographic characteristics associated with MRH in older people taking BP-lowering drugs for whatever indication they were prescribed. METHODS: The PRIME (prospective study to develop a model to stratify the risk of MRH in hospitalised elderly patients in the UK) study investigating the incidence and cost of MRH in older people across Southern England. Adults ≥65 years were recruited from five teaching hospitals at hospital discharge and followed up for 8 weeks. Telephone interviews with study participants, review of primary care records and hospital readmissions were undertaken to identify MRH. PRIME study participants taking BP-lowering drugs (as defined by National Institute for Health and Care Excellence hypertension guidelines) were included in this analysis. RESULTS: One hundred and four (12%) study patients experienced a total of 153 MRH events associated with BP-lowering drugs. Patients on four BP-lowering drugs were five times more likely to experience MRH compared to those taking one medication (OR 4.96; 95%CI 1.63-15.13; P = 0.01). Most MRH events were classified 'serious' (80%, n = 123), requiring dose change or treatment cessation. Almost half of MRH were potentially preventable (49%, n = 75). CONCLUSION: Polypharmacy from BP-lowering drugs in older people is associated with preventable harm. Decisions around cardiovascular risk reduction should be carefully considered in view of MRH arising from BP-lowering drugs.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Idoso , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea , Humanos , Alta do Paciente , Estudos Prospectivos
14.
Age Ageing ; 51(3)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35353136

RESUMO

OBJECTIVES: To determine the association between frailty and medication-related harm requiring healthcare utilisation. DESIGN: Prospective observational cohort study. SETTING: Six primary and five secondary care sites across South East England, September 2013-November 2015. PARTICIPANTS: One thousand and two hundred and eighty participants, ≥65 years old, who were due for discharge from general medicine and older persons' wards following an acute episode of care. Exclusion criteria were limited life expectancy, transfer to another hospital and consent not gained. MAIN OUTCOME MEASURES: Medication-related harm requiring healthcare utilisation (including primary, secondary or tertiary care consultations related to MRH), including adverse drug reactions, non-adherence and medication error determined via the review of data from three sources: patient/carer reports gathered through a structured telephone interview; primary care medical record review; and prospective consultant-led review of readmission to recruiting hospital. Frailty was measured using a Frailty Index, developed using a standardised approach. Marginal estimates were obtained from logistic regression models to examine how probabilities of healthcare service use due to medication-related harm were associated with increasing number of medicines and frailty. RESULTS: Healthcare utilisation due to medication-related harm was significantly associated with frailty (OR = 10.06, 95% CI 2.06-49.26, P = 0.004), independent of age, gender, and number of medicines. With increasing frailty, the need for healthcare use as a result of MRH increases from a probability of around 0.2-0.4. This is also the case for the number of medicines. CONCLUSIONS: Frailty is associated with MRH, independent of polypharmacy. Reducing the burden of frailty through an integrated health and social care approach, alongside strategies to reduce inappropriate polypharmacy, may reduce MRH related healthcare utilisation.


Assuntos
Fragilidade , Polimedicação , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Humanos , Alta do Paciente , Estudos Prospectivos
15.
J Obstet Gynaecol ; 42(7): 2652-2658, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35980980

RESUMO

This study examines whether a change in the criteria for genetic testing for ovarian cancer risk changed the nature of referrals into our Familial Cancer service. This is a retrospective review of 273 women who underwent risk reducing surgery (RRS). The primary outcome was to establish whether there was an increase in women having RRS with a confirmed genetic mutation. Secondary outcomes included the incidence of occult cancer and of subsequent primary peritoneal cancer. The results showed an increase in women being offered RRS based on genetic diagnosis; 91% versus 32% before the criteria change. Four occult malignancies (1.5%) and two peritoneal cancers (0.7%) were noted.We have demonstrated a change in the nature of referrals to the familial cancer service from perceived risk to genetic diagnosis. We can now counsel women more accurately. With a defined risk we are enabling them to make an informed decision regarding risk reduction.


Assuntos
Genes BRCA1 , Neoplasias Ovarianas , Feminino , Humanos , Estudos Retrospectivos , Genes BRCA2 , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Testes Genéticos , Mutação , Encaminhamento e Consulta , Predisposição Genética para Doença
16.
Br J Dermatol ; 184(5): 913-922, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32730675

RESUMO

BACKGROUND: Atopic dermatitis (AD) arises from a complex interaction between an impaired epidermal barrier, environmental exposures, and the infiltration of T helper (Th)1/Th2/Th17/Th22 T cells. Transcriptomic analysis has advanced our understanding of gene expression in cells and tissues. However, molecular quantitation of cytokine transcripts does not predict the importance of a specific pathway in AD or cellular responses to different inflammatory stimuli. OBJECTIVES: To understand changes in keratinocyte transcriptomic programmes in human cutaneous disease during development of inflammation and in response to treatment. METHODS: We performed in silico deconvolution of the whole-skin transcriptome. Using co-expression clustering and machine-learning tools, we resolved the gene expression of bulk skin (seven datasets, n = 406 samples), firstly, into keratinocyte phenotypes identified by unsupervised clustering and, secondly, into 19 cutaneous cell signatures of purified populations from publicly available datasets. RESULTS: We identify three unique transcriptomic programmes in keratinocytes - KC1, KC2 and KC17 - characteristic of immune signalling from disease-associated Th cells. We cross-validate those signatures across different skin inflammatory conditions and disease stages and demonstrate that the keratinocyte response during treatment is therapy dependent. Broad-spectrum treatment with ciclosporin ameliorated the KC17 response in AD lesions to a nonlesional immunophenotype, without altering KC2. Conversely, the specific anti-Th2 therapy, dupilumab, reversed the KC2 immunophenotype. CONCLUSIONS: Our analysis of transcriptomic signatures in cutaneous disease biopsies reveals the effect of keratinocyte programming in skin inflammation and suggests that the perturbation of a single axis of immune signal alone may be insufficient to resolve keratinocyte immunophenotype abnormalities.


Assuntos
Dermatite Atópica , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/genética , Humanos , Queratinócitos , Aprendizado de Máquina , Pele , Células Th2 , Transcriptoma
17.
Philos Trans A Math Phys Eng Sci ; 379(2209): 20200336, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34510928

RESUMO

This paper reports a simple way to produce porous graphitic carbons from a wide range of lignocellulosic biomass sources, including nut shells, softwood sawdust, seed husks and bamboo. Biomass precursors are milled and sieved to produce fine powders and are then converted to porous graphitic carbons by iron-catalysed graphitization. Graphitizing the raw (unmilled) biomass creates carbons that are diverse in their porosity and adsorption properties. This is due to the inability of the iron catalyst precursor to penetrate the structure of dense biomass material. Milling enables much more efficient impregnation of the biomass and produces carbons with homogeneous properties. Lignocellulosic biomass (particularly waste biomass) is an attractive precursor to technologically important porous graphitic carbons as it is abundant and renewable. This simple method for preparing the biomass enables a wide range of biomass sources to be used to produce carbons with homogeneous properties. This article is part of the theme issue 'Bio-derived and bioinspired sustainable advanced materials for emerging technologies (part 2)'.

18.
Philos Trans A Math Phys Eng Sci ; 379(2189): 20200052, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33280559

RESUMO

Inertial confinement fusion approaches involve the creation of high-energy-density states through compression. High gain scenarios may be enabled by the beneficial heating from fast electrons produced with an intense laser and by energy containment with a high-strength magnetic field. Here, we report experimental measurements from a configuration integrating a magnetized, imploded cylindrical plasma and intense laser-driven electrons as well as multi-stage simulations that show fast electrons transport pathways at different times during the implosion and quantify their energy deposition contribution. The experiment consisted of a CH foam cylinder, inside an external coaxial magnetic field of 5 T, that was imploded using 36 OMEGA laser beams. Two-dimensional (2D) hydrodynamic modelling predicts the CH density reaches [Formula: see text], the temperature reaches 920 eV and the external B-field is amplified at maximum compression to 580 T. At pre-determined times during the compression, the intense OMEGA EP laser irradiated one end of the cylinder to accelerate relativistic electrons into the dense imploded plasma providing additional heating. The relativistic electron beam generation was simulated using a 2D particle-in-cell (PIC) code. Finally, three-dimensional hybrid-PIC simulations calculated the electron propagation and energy deposition inside the target and revealed the roles the compressed and self-generated B-fields play in transport. During a time window before the maximum compression time, the self-generated B-field on the compression front confines the injected electrons inside the target, increasing the temperature through Joule heating. For a stronger B-field seed of 20 T, the electrons are predicted to be guided into the compressed target and provide additional collisional heating. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

19.
Am J Physiol Lung Cell Mol Physiol ; 319(1): L39-L44, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32491949

RESUMO

The rapid emergence and subsequent global dissemination of SARS-CoV-2 disease (COVID-19) has resulted in over 4 million cases worldwide. The disease has a marked predilection for adults, and children are relatively spared. Understanding the age-based differences in pathophysiological pathways and processes relevant to the onset and progression of disease both in the clinical course and in experimental disease models may hold the key to the identification of therapeutic targets. The differences in the clinical course are highlighted by the lack of progression of the SARS-CoV-2 infection beyond mild symptoms in a majority of children, whereas in adults the disease progresses to acute lung injury and an acute respiratory distress syndrome (ARDS)-like phenotype with high mortality. The pathophysiological mechanisms leading to decreased lung injury in children may involve the decreased expression of the mediators necessary for viral entry into the respiratory epithelium and differences in the immune system responses in children. Specifically, decreased expression of proteins, including angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) in the airway epithelium in children may prevent viral entry. The immune system differences may include a relative preponderance of CD4+ T cells, decreased neutrophil infiltration, decreased production of proinflammatory cytokines, and increased production of immunomodulatory cytokines in children compared with adults. Notably, the developing lung in children may have a greater capacity to recover and repair after viral infection. Understanding the relative contributions of the above processes to the protective phenotype in the developing lung can guide the trial of the appropriate therapies in adults.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Adulto , Distribuição por Idade , Enzima de Conversão de Angiotensina 2 , COVID-19 , Criança , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Citocinas/sangue , Humanos , Pandemias , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , SARS-CoV-2 , Serina Endopeptidases/metabolismo
20.
Clin Immunol ; 214: 108375, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32135275

RESUMO

Up to 80% of juvenile-onset systemic lupus erythematosus (jSLE) patients develop lupus nephritis (LN) that affects treatment and prognosis. Easily accessible biomarkers do not exist to reliably diagnose LN, leaving kidney biopsies as the gold-standard. Calcium-binding S100 proteins are expressed by innate immune cells and epithelia and may act as biomarkers in systemic inflammatory conditions. We quantified S100 proteins in the serum and urine of jSLE patients, matched healthy and inflammatory (IgA vasculitis) controls. Serum S100A8/A9, and serum and urine S100A12 are increased in jSLE patients when compared to controls. Furthermore, serum S100A8/A9, and serum and urine S100A12 are increased in jSLE patients with active as compared to patients with inactive/no LN. No differences in S100A4 levels were seen between groups. This study demonstrates potential promise for S100A8/A9 and S100A12 as biomarkers for jSLE and active LN. Findings require to be confirmed and tested prospectively in independent and larger multi-ethnic cohorts.


Assuntos
Calgranulina A/sangue , Calgranulina B/sangue , Calgranulina B/urina , Nefrite Lúpica/sangue , Nefrite Lúpica/urina , Proteína S100A12/sangue , Proteína S100A12/urina , Adolescente , Idade de Início , Biomarcadores/sangue , Biomarcadores/urina , Calgranulina A/análise , Estudos de Casos e Controles , Criança , Pré-Escolar , Creatinina/sangue , Feminino , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/urina , Humanos , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Prognóstico , Índice de Gravidade de Doença , Adulto Jovem
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