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1.
Nature ; 628(8009): 788-794, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38538788

RESUMO

Biodiversity faces unprecedented threats from rapid global change1. Signals of biodiversity change come from time-series abundance datasets for thousands of species over large geographic and temporal scales. Analyses of these biodiversity datasets have pointed to varied trends in abundance, including increases and decreases. However, these analyses have not fully accounted for spatial, temporal and phylogenetic structures in the data. Here, using a new statistical framework, we show across ten high-profile biodiversity datasets2-11 that increases and decreases under existing approaches vanish once spatial, temporal and phylogenetic structures are accounted for. This is a consequence of existing approaches severely underestimating trend uncertainty and sometimes misestimating the trend direction. Under our revised average abundance trends that appropriately recognize uncertainty, we failed to observe a single increasing or decreasing trend at 95% credible intervals in our ten datasets. This emphasizes how little is known about biodiversity change across vast spatial and taxonomic scales. Despite this uncertainty at vast scales, we reveal improved local-scale prediction accuracy by accounting for spatial, temporal and phylogenetic structures. Improved prediction offers hope of estimating biodiversity change at policy-relevant scales, guiding adaptive conservation responses.


Assuntos
Biodiversidade , Incerteza , Animais , Conservação dos Recursos Naturais/métodos , Conservação dos Recursos Naturais/tendências , Conjuntos de Dados como Assunto , Filogenia , Análise Espaço-Temporal , Fatores de Tempo
2.
Phys Rev Lett ; 131(17): 172501, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37955509

RESUMO

The boundaries of the chart of nuclides contain exotic isotopes that possess extreme proton-to-neutron asymmetries. Here we report on strong evidence of ^{9}N, one of the most exotic proton-rich isotopes where more than one half of its constitute nucleons are unbound. With seven protons and two neutrons, this extremely proton-rich system would represent the first-known example of a ground-state five-proton emitter. The invariant-mass spectrum of its decay products can be fit with two peaks whose energies are consistent with the theoretical predictions of an open-quantum-system approach; however, we cannot rule out the possibility that only a single resonancelike peak is present in the spectrum.

3.
Phys Rev Lett ; 126(13): 132501, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33861136

RESUMO

A ^{13}F resonance was observed following a charge-exchange reaction between a fast ^{13}O beam and a ^{9}Be target. The resonance was found in the invariant-mass distribution of 3p+^{10}C events and probably corresponds to a 5/2^{+} excited state. The ground state was also expected to be populated, but was not resolved from the background. The observed level decays via initial proton emissions to both the ground and first 2^{+} state of ^{12}O, which subsequently undergo 2p decay. In addition, there may also be a significant proton decay branch to the second 2^{+} level in ^{12}O. The wave function associated with the observed level may be collectivized due to coupling to the continuum as is it located just above the threshold for proton decay to the 2_{2}^{+} state of ^{12}O.

4.
Phys Rev Lett ; 122(12): 122501, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30978039

RESUMO

The structure of the extremely proton-rich nucleus _{8}^{11}O_{3}, the mirror of the two-neutron halo nucleus _{3}^{11}Li_{8}, has been studied experimentally for the first time. Following two-neutron knockout reactions with a ^{13}O beam, the ^{11}O decay products were detected after two-proton emission and used to construct an invariant-mass spectrum. A broad peak of width ∼3.4 MeV was observed. Within the Gamow coupled-channel approach, it was concluded that this peak is a multiplet with contributions from the four lowest ^{11}O resonant states: J^{π}=3/2_{1}^{-}, 3/2_{2}^{-}, 5/2_{1}^{+}, and 5/2_{2}^{+}. The widths and configurations of these states show strong, nonmonotonic dependencies on the depth of the p-^{9}C potential. This unusual behavior is due to the presence of a broad threshold resonant state in ^{10}N, which is an analog of the virtual state in ^{10}Li in the presence of the Coulomb potential. After optimizing the model to the data, only a moderate isospin asymmetry between ground states of ^{11}O and ^{11}Li was found.

5.
Phys Rev Lett ; 119(23): 232501, 2017 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-29286688

RESUMO

We study the sequential breakup of E/A=24.0 MeV ^{7}Li projectiles excited through inelastic interactions with C, Be, and Al target nuclei. For peripheral events that do not excite the target, we find very large spin alignment of the excited ^{7}Li projectiles longitudinal to the beam axis. This spin alignment is independent of the target used, and we propose a simple alignment mechanism that arises from an angular-momentum-excitation-energy mismatch. This mechanism is independent of the potential used for scattering and should be present in many scattering experiments.

6.
Psychol Med ; 47(14): 2528-2539, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28446253

RESUMO

BACKGROUND: The present research aimed to investigate the efficacy of a multifaceted intervention that included motivational interviewing (MI) and psychoeducation in improving medication adherence (MA) among patients with bipolar disorder (BD). METHOD: A multicenter, cluster randomized, observer-blind, controlled, parallel-group trial was conducted in ten academic centers in Iran. Patients with BD were randomly assigned to the experimental group (EXP; n = 136) or the usual care group (UC; n = 134). The EXP group received five sessions of MI and psychoeducation together with their family members. The primary outcome measure was changes in scores on the Medication Adherence Rating Scale from baseline to 6 months post-intervention. Other outcome measures included serum levels of mood stabilizers, clinical symptoms, quality of life, as well as measures of intention, beliefs about medicine, perceived behavioral control, automaticity, action and coping planning, and adverse reactions. RESULTS: Medication adherence improved over time in both groups, but patients in the EXP group improved more (baseline score: 6.03; score at the sixth month: 9.55) than patients in the UC group (baseline score: 6.17; score at the sixth month: 6.67). In addition, patients in the EXP group showed greater improvement than patients in the UC group in almost all secondary outcomes 6 months following the intervention. CONCLUSIONS: Multifaceted interventions that include motivational-interviewing and psychoeducation can significantly improve MA and clinical and functional outcomes in patients with BD. TRIAL REGISTRATION NUMBER: The trial was registered with theClinicalTrials.gov database (NCT02241863) https://clinicaltrials.gov/ct2/show/NCT02241863.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Promoção da Saúde/métodos , Adesão à Medicação/psicologia , Entrevista Motivacional/métodos , Avaliação de Resultados em Cuidados de Saúde , Psicoterapia/métodos , Tranquilizantes , Adulto , Assistência ao Convalescente , Transtorno Bipolar/fisiopatologia , Feminino , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Método Simples-Cego , Tranquilizantes/sangue
7.
Diabet Med ; 33(6): 723-33, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27194172

RESUMO

Diabetes disproportionately affects disadvantaged populations. Eighty percent of deaths directly caused by diabetes occurred in low- and middle-income countries. In high-income countries, there are marked disparities in diabetes control among racial/ethnic minorities and those with low socio-economic status. Innovative, effective and cost-effective strategies are needed to improve diabetes outcomes in these populations. Technological advances, peer educators and community health workers have expanded methodologies to reach, educate and monitor individuals with diabetes. In the present manuscript we review the outcomes of these strategies, and describe the barriers to and facilitators of these approaches for improving diabetes outcomes.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Terapias em Estudo/estatística & dados numéricos , Adulto , Criança , Serviços de Saúde Comunitária/economia , Serviços de Saúde Comunitária/estatística & dados numéricos , Agentes Comunitários de Saúde/economia , Agentes Comunitários de Saúde/estatística & dados numéricos , Custos e Análise de Custo , Diabetes Mellitus Tipo 1/economia , Diabetes Mellitus Tipo 2/economia , Saúde Global/economia , Saúde Global/estatística & dados numéricos , Disparidades em Assistência à Saúde/economia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Humanos , Internet/economia , Internet/estatística & dados numéricos , Aplicativos Móveis/economia , Aplicativos Móveis/estatística & dados numéricos , Educação de Pacientes como Assunto/economia , Educação de Pacientes como Assunto/estatística & dados numéricos , Consulta Remota/economia , Consulta Remota/estatística & dados numéricos , Mídias Sociais/economia , Mídias Sociais/estatística & dados numéricos , Fatores Socioeconômicos , Telefone/economia , Telefone/estatística & dados numéricos , Terapias em Estudo/economia , Terapia Assistida por Computador/economia , Terapia Assistida por Computador/estatística & dados numéricos , Resultado do Tratamento , Populações Vulneráveis
8.
Clin Exp Allergy ; 45(1): 154-63, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25200568

RESUMO

BACKGROUND: Infancy is a developmental stage with heightened susceptibility to environmental influences on the risk of chronic childhood disease. Few birth cohort studies have detailed measures of fungal diversity data in infants' bedrooms, limiting the potential to measure long-term associations of these complex exposures with development of asthma or allergy. OBJECTIVE: We evaluated the relation of home fungal levels in infancy to repeated measures of wheeze and development of asthma and rhinitis by age 13, and sensitization by age 12 years. METHODS: In the Epidemiology of Home Allergens and Asthma prospective birth cohort study, we recruited 408 children with family history of allergic disease or asthma. When children were aged 2-3 months, we measured culturable fungi in bedroom air and dust, and in outdoor air. Main outcomes included ascertainment of symptoms/disease onset by questionnaire from birth through age 13. We estimated hazard ratios and, for wheeze and sensitization, odds ratios for an interquartile increase in log-transformed fungal concentrations, adjusting for other outcome predictors and potential confounders. RESULTS: Elevated levels of yeasts in bedroom floor dust were associated with reduced: i) wheeze at any age; ii) fungal sensitization; and iii) asthma development by age 13 (hazard ratio (HR) = 0.86; 95% confidence interval (CI), [0.75 to 0.98]). Outdoor airborne Cladosporium and dustborne Aspergillus predicted increased rhinitis. Risk of fungal sensitization by age 12, in response to environmental Alternaria and Aspergillus, was elevated in children with a maternal history of fungal sensitization. CONCLUSIONS AND CLINICAL RELEVANCE: Despite the irritant and allergenic properties of fungi, early-life elevated dust yeast exposures or their components may be protective against allergy and asthma in children at risk for these outcomes. Ascertainment of fungal components associated with immunoprotective effects may have therapeutic relevance for asthma.


Assuntos
Poluição do Ar em Ambientes Fechados , Asma , Fungos , Asma/epidemiologia , Asma/etiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos
9.
Psychol Med ; 45(3): 615-21, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25088280

RESUMO

BACKGROUND: The past two decades have seen a great improvement in the care of people with Prader-Willi syndrome (PWS), particularly with regard to control of diet and behaviour management. Has this affected mortality rates or thrown up new issues regarding premature ageing or dementia? We investigated two aspects of ageing in people with PWS: (1) an estimate of mortality over 9 years in a cohort of people with PWS, originally recruited in 1998-2000; and (2) premature ageing or dementia in people aged ⩾40 years. METHOD: (1) A follow-up of the population-based 1998-2000 cohort to investigate the subsequent mortality rate; and (2) the recruitment and structured assessment of all members of the Prader-Willi Syndrome Association UK (PWSA-UK) aged ⩾40 years who agreed to participate. RESULTS: Follow-up of the population-based 1998-2000 cohort gave a mortality rate of at least 7/62 over 9 years (1.25% per annum; 20 untraced), age at death was between 13 and 59 years. Twenty-six members of the PWSA-UK aged ⩾40 years were recruited, 18 of whom had a genetic diagnosis (gd) of PWS. Twenty-two (14 gd) showed no evidence of dementia. Four, with possible symptoms, are described in more detail; all are female, of maternal uniparental disomy (mUPD) genetic subtype, or have a disomic region, and all have a long history of psychotic illness. CONCLUSIONS: The mortality rate in people with PWS seems to be declining. The subgroup of people with PWS due to UPD or disomic region with female gender and a history of psychosis may be at risk of early onset dementia.


Assuntos
Envelhecimento , Doença de Alzheimer/epidemiologia , Síndrome de Prader-Willi/complicações , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/mortalidade , Adolescente , Adulto , Senilidade Prematura , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Dissomia Uniparental , Reino Unido/epidemiologia , Adulto Jovem
10.
Clin Exp Allergy ; 44(12): 1546-57, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25220646

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) decrease airway eosinophilia, airway hyperresponsiveness (AHR), and remodelling in murine models of acutely induced asthma. We hypothesized that MSCs would diminish these hallmark features in a chronic feline asthma model. OBJECTIVE: To document effects of allogeneic, adipose-derived MSCs on airway inflammation, AHR, and remodelling over time and investigate mechanisms by which MSCs alter local and systemic immunologic responses in chronic experimental feline allergic asthma. METHODS: Cats with chronic, experimentally induced asthma received six intravenous infusions of MSCs (0.36-2.5 × 10E7 MSCs/infusion) or placebo bimonthly at the time of study enrollment. Cats were evaluated at baseline and longitudinally for 1 year. Outcome measures included: bronchoalveolar lavage fluid cytology to assess airway eosinophilia, pulmonary mechanics and clinical scoring to assess AHR, and thoracic computed tomographic (CT) scans to assess structural changes (airway remodelling). CT scans were evaluated using a scoring system for lung attenuation (LA) and bronchial wall thickening (BWT). To assess mechanisms of MSC action, immunologic assays including allergen-specific IgE, cellular IL-10 production, and allergen-specific lymphocyte proliferation were performed. RESULTS: There were no differences between treatment groups or over time with respect to airway eosinophilia or AHR. However, significantly lower LA and BWT scores were noted in CT images of MSC-treated animals compared to placebo-treated cats at month 8 of the study (LA P = 0.0311; BWT P = 0.0489). No differences were noted between groups in the immunologic assays. CONCLUSIONS AND CLINICAL RELEVANCE: When administered after development of chronic allergic feline asthma, MSCs failed to reduce airway inflammation and AHR. However, repeated administration of MSCs at the start of study did reduce computed tomographic measures of airway remodelling by month 8, although the effect was not sustained at month 12. Further study of MSC therapy including repeated MSC administration is warranted to assess impact on remodelling in chronic asthma.


Assuntos
Asma/imunologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Remodelação das Vias Aéreas , Alérgenos/imunologia , Animais , Asma/diagnóstico , Asma/fisiopatologia , Asma/terapia , Hiper-Reatividade Brônquica/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Gatos , Modelos Animais de Doenças , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Interleucina-10/metabolismo , Ativação Linfocitária/imunologia , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células-Tronco Mesenquimais/metabolismo , Tomografia Computadorizada por Raios X
11.
Psychol Med ; 44(11): 2431-5, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24330817

RESUMO

BACKGROUND: People with Prader-Willi syndrome (PWS), a genetically defined developmental disorder, are at increased risk of developing psychotic illness. This is particularly the case for those with a genetic subtype of PWS called maternal uniparental disomy (mUPD), where rates of psychosis are more than 60% by early adult life. Little is known about the long-term course of their disorder. METHOD: Individuals who had had episodes of psychosis or were at increased risk of developing psychosis due to their genetic subtype and had taken part in a previous study were contacted. Ten people were untraceable or deceased, leaving a total of 38 potential participants. Of these, 28 agreed to take part in a follow-up interview or complete a questionnaire about their mental health and medication. This represented 20/35 (57.1%) people from the original study who had had psychosis and 8/13 (61.5%) people who were at risk due to their genetic subtype. They were thought to be representative of those groups as a whole based on IQ and number of episodes of psychosis. RESULTS: Two individuals had had recurrent episodes of psychosis while all others remained well. There were no new-onset cases of psychosis in those at risk. Individuals with PWS remained on high levels of psychiatric medication throughout the follow-up period. CONCLUSIONS: Recurrent episodes of psychosis may be rare in people with PWS once stability has been achieved in the management of their illness. We speculate that this may be due to the protective influence of medication.


Assuntos
Síndrome de Prader-Willi/genética , Transtornos Psicóticos/genética , Adulto , Comorbidade , Seguimentos , Humanos , Pessoa de Meia-Idade , Síndrome de Prader-Willi/epidemiologia , Transtornos Psicóticos/epidemiologia , Risco , Adulto Jovem
12.
Br J Dermatol ; 171(2): 332-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24665869

RESUMO

BACKGROUND: Vitiligo can be associated with high levels of distress, yet there are currently no self-help interventions available. OBJECTIVES: To describe the initial development of a psychosocial self-help intervention designed to reduce social anxiety associated with vitiligo. Also to examine whether including a planning exercise, aimed at increasing use of the intervention (termed implementation intentions), has the potential to achieve a clinically significant reduction in distress. METHODS: Participants (n = 75) were randomized to one of three groups: cognitive behavioural self-help (CBSH), CBSH augmented with implementation intentions (CBSH+), or no intervention. Participants were assessed at baseline and after 8 weeks on measures of social anxiety, anxiety and depression, and appearance-related concern. The two intervention groups also completed a questionnaire evaluating their use of, and satisfaction with, the intervention. RESULTS: High levels of social anxiety and concern over appearance were reported. Twenty-four per cent of participants in the CBSH+ group experienced clinically significant change on the measure of social anxiety compared with 8% in the CBSH group and 0% in the control group. In addition, 58% of the control group deteriorated during the study period. There were no significant differences between the conditions on the other outcome measures. Participants reported that the self-help leaflets were helpful. CONCLUSIONS: The findings demonstrate that augmented CBSH provides a relatively simple and accessible intervention that can result in a clinically significant reduction in social anxiety. The augmented intervention has potential and might be further developed and evaluated in subsequent trials.


Assuntos
Transtornos de Ansiedade/prevenção & controle , Terapia Cognitivo-Comportamental/métodos , Grupos de Autoajuda , Vitiligo/psicologia , Adolescente , Adulto , Idoso , Transtornos de Ansiedade/etiologia , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Resultado do Tratamento , Adulto Jovem
13.
Am J Physiol Cell Physiol ; 305(4): C427-35, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23784541

RESUMO

A collagenase-proteinase mixture was used to isolate airway smooth muscle cells (ASMC) from rabbit bronchi, and membrane currents were recorded using the whole cell patch-clamp technique. Stepping from -100 mV to a test potential of -40 mV evoked a fast voltage-dependent Na(+) current, sometimes with an amplitude of several nanoamperes. The current disappeared within 15 min of exposure to papain + DTT (n = 6). Comparison of the current in ASMC with current mediated by NaV1.5 α-subunits expressed in human embryonic kidney cells revealed similar voltage dependences of activation (V1/2 = -42 mV for NaV1.5) and sensitivities to TTX (IC50 = 1.1 and 1.2 µM for ASMC and NaV1.5, respectively). The current in ASMC was also blocked by lidocaine (IC50 = 160 µM). Although veratridine, an agonist of voltage-gated Na(+) channels, reduced the peak current by 33%, it slowed inactivation, resulting in a fourfold increase in sustained current (measured at 25 ms after onset). In current-clamp mode, veratridine prolonged evoked action potentials from 37 ± 9 to 1,053 ± 410 ms (n = 8). Primers for NaV1.2-1.9 were used to amplify mRNA from groups of ∼20 isolated ASMC and from whole bronchial tissue by RT-PCR. Transcripts for NaV1.2, NaV1.3, and NaV1.5-1.9 were detected in whole tissue, but only NaV1.2 and NaV1.5 were detected in single cells. We conclude that freshly dispersed rabbit ASMC express a fast voltage-gated Na(+) current that is mediated mainly by the NaV1.5 subtype.


Assuntos
Brônquios/metabolismo , Miócitos de Músculo Liso/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Animais , Brônquios/citologia , Brônquios/efeitos dos fármacos , Separação Celular/métodos , Regulação da Expressão Gênica , Células HEK293 , Humanos , Ativação do Canal Iônico , Cinética , Potenciais da Membrana , Canal de Sódio Disparado por Voltagem NAV1.5/efeitos dos fármacos , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Técnicas de Patch-Clamp , RNA Mensageiro/metabolismo , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Bloqueadores dos Canais de Sódio/farmacologia , Transfecção
14.
J Evol Biol ; 26(9): 2063-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23786459

RESUMO

Lower visibility of female scientists, compared to male scientists, is a potential reason for the under-representation of women among senior academic ranks. Visibility in the scientific community stems partly from presenting research as an invited speaker at organized meetings. We analysed the sex ratio of presenters at the European Society for Evolutionary Biology (ESEB) Congress 2011, where all abstract submissions were accepted for presentation. Women were under-represented among invited speakers at symposia (15% women) compared to all presenters (46%), regular oral presenters (41%) and plenary speakers (25%). At the ESEB congresses in 2001-2011, 9-23% of invited speakers were women. This under-representation of women is partly attributable to a larger proportion of women, than men, declining invitations: in 2011, 50% of women declined an invitation to speak compared to 26% of men. We expect invited speakers to be scientists from top ranked institutions or authors of recent papers in high-impact journals. Considering all invited speakers (including declined invitations), 23% were women. This was lower than the baseline sex ratios of early-mid career stage scientists, but was similar to senior scientists and authors that have published in high-impact journals. High-quality science by women therefore has low exposure at international meetings, which will constrain Evolutionary Biology from reaching its full potential. We wish to highlight the wider implications of turning down invitations to speak, and encourage conference organizers to implement steps to increase acceptance rates of invited talks.


Assuntos
Evolução Biológica , Congressos como Assunto/tendências , Pesquisadores/estatística & dados numéricos , Sexismo/tendências , Feminino , Humanos , Pesquisadores/tendências
15.
Biochim Biophys Acta Mol Cell Res ; 1870(6): 119479, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37100352

RESUMO

BACKGROUND: The large extracellular matrix protein SVEP1 mediates cell adhesion via integrin α9ß1. Recent studies have identified an association between a missense variant in SVEP1 and increased risk of coronary artery disease (CAD) in humans and in mice Svep1 deficiency alters the development of atherosclerotic plaques. However how SVEP1 functionally contributes to CAD pathogenesis is not fully understood. Monocyte recruitment and differentiation to macrophages is a key step in the development of atherosclerosis. Here, we investigated the requirement for SVEP1 in this process. METHODS: SVEP1 expression was measured during monocyte-macrophage differentiation in primary monocytes and THP-1 human monocytic cells. SVEP1 knockout THP-1 cell lines and the dual integrin α4ß1/α9ß1 inhibitor, BOP, were utilised to investigate the effect of these proteins in THP-1 cell adhesion, migration and cell spreading assays. Subsequent activation of downstream integrin signalling intermediaries was quantified by western blotting. RESULTS: SVEP1 gene expression increases in monocyte to macrophage differentiation in human primary monocytes and THP-1 cells. Using two SVEP1 knockout THP-1 cells we observed reduction in monocyte adhesion, migration, and cell spreading compared to control cells. Similar results were found with integrin α4ß1/α9ß1 inhibition. We demonstrate reduced activity of Rho and Rac1 in SVEP1 knockout THP-1 cells. CONCLUSIONS: SVEP1 regulates monocyte recruitment and differentiation phenotypes through an integrin α4ß1/α9ß1 dependent mechanism. GENERAL SIGNIFICANCE: These results describe a novel role for SVEP1 in monocyte behaviour relevant to CAD pathophysiology.


Assuntos
Integrina alfa4beta1 , Monócitos , Humanos , Moléculas de Adesão Celular/metabolismo , Diferenciação Celular/genética , Integrina alfa4beta1/metabolismo , Macrófagos/metabolismo
16.
Rev Sci Instrum ; 94(5)2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37129462

RESUMO

Accurate understanding of x-ray diagnostics is crucial for both interpreting high-energy-density experiments and testing simulations through quantitative comparisons. X-ray diagnostic models are complex. Past treatments of individual x-ray diagnostics on a case-by-case basis have hindered universal diagnostic understanding. Here, we derive a general formula for modeling the absolute response of non-focusing x-ray diagnostics, such as x-ray imagers, one-dimensional space-resolved spectrometers, and x-ray power diagnostics. The present model is useful for both data modeling and data processing. It naturally accounts for the x-ray crystal broadening. The new model verifies that standard approaches for a crystal response can be good approximations, but they can underestimate the total reflectivity and overestimate spectral resolving power by more than a factor of 2 in some cases near reflectivity edge features. We also find that a frequently used, simplified-crystal-response approximation for processing spectral data can introduce an absolute error of more than an order of magnitude and the relative spectral radiance error of a factor of 3. The present model is derived with straightforward geometric arguments. It is more general and is recommended for developing a unified picture and providing consistent treatment over multiple x-ray diagnostics. Such consistency is crucial for reliable multi-objective data analyses.

17.
Rev Sci Instrum ; 94(3): 031102, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37012753

RESUMO

The Z machine is a current driver producing up to 30 MA in 100 ns that utilizes a wide range of diagnostics to assess accelerator performance and target behavior conduct experiments that use the Z target as a source of radiation or high pressures. We review the existing suite of diagnostic systems, including their locations and primary configurations. The diagnostics are grouped in the following categories: pulsed power diagnostics, x-ray power and energy, x-ray spectroscopy, x-ray imaging (including backlighting, power flow, and velocimetry), and nuclear detectors (including neutron activation). We will also briefly summarize the primary imaging detectors we use at Z: image plates, x-ray and visible film, microchannel plates, and the ultrafast x-ray imager. The Z shot produces a harsh environment that interferes with diagnostic operation and data retrieval. We term these detrimental processes "threats" of which only partial quantifications and precise sources are known. We summarize the threats and describe techniques utilized in many of the systems to reduce noise and backgrounds.

18.
J Neurol Neurosurg Psychiatry ; 83(1): 109-14, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21849340

RESUMO

BACKGROUND: The human prion diseases are a group of universally fatal neurodegenerative disorders associated with the auto-catalytic misfolding of the normal cell surface prion protein (PrP). Mutations causative of inherited human prion disease (IPD) include an insertion of six additional octapeptide repeats (6-OPRI) and a missense mutation (P102L) with large families segregating for each mutation residing in southern England. Here we report for the first time the neuropsychological and clinical assessments in these two groups. METHOD: The cognitive profiles addressing all major domains were obtained for 26 patients (18 6-OPRI, 8 P102L) and the cortical thickness determined using 1.5T MRI in a subset of 10 (six 6-OPRI, four P102L). RESULTS: The cognitive profiles were different in patients with the two mutations in the symptomatic phase of the disease. The 6-OPRI group had lower premorbid optimal levels of functioning (assessed on the NART) than the P102L group. In the symptomatic phase of the disease the 6-OPRI patients had significantly more executive dysfunction than the P102L group and were more impaired on tests of perception and nominal functions. There was anecdotal evidence of low premorbid social performance in the 6-OPRI but not P102L patients. Cortical thinning distribution correlated with the neuropsychological profile in the 6-OPRI group principally involving the parietal, occipital and posterior frontal regions. The small number of patients in the P102L group precluded statistical comparison between the groups. CONCLUSIONS: The 6-OPRI patients had more widespread and severe cognitive dysfunction than the P102L group and this correlated with cortical thinning distribution.


Assuntos
Encéfalo/patologia , Mutagênese Insercional/genética , Doenças Priônicas/genética , Príons/genética , Adulto , Transtornos Cognitivos/etiologia , Função Executiva , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Neuroimagem , Testes Neuropsicológicos , Doenças Priônicas/complicações , Doenças Priônicas/patologia , Reino Unido , Adulto Jovem
19.
Br J Dermatol ; 167(5): 970-9, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22924999

RESUMO

Skin conditions can be associated with heightened levels of psychological morbidity, suggesting the need for psychological interventions. A number of specific interventions (such as habit reversal) have been developed. However, to date, there has not been a systematic review of the effectiveness of psychological interventions. We sought to systematically evaluate the effectiveness of psychological interventions designed to improve the severity of and adjustment to skin conditions in adults. Database, archival and citation searches were conducted. Studies were included if participants were allocated to either a psychological intervention (excluding educational interventions and complementary therapies) or a comparison condition, and if they measured outcomes relevant to the skin condition. Twenty-two studies met these inclusion criteria. Effect sizes for each intervention were computed and we also coded a number of potential moderators of intervention efficacy. Psychological interventions were found to have a medium-sized effect on skin conditions (g = 0·54). The type of skin condition, age of sample, nature of the intervention, time interval between the end of the intervention and follow-up, and type of outcome measure all moderated the effect of interventions on outcomes. For example, interventions had a medium effect on the severity of the condition (g = 0·40) and psychosocial outcomes (g = 0·53), and a medium-to-large effect on itch/scratch reactions (g = 0·67). Psychological interventions are beneficial for people with skin conditions. However, more research is needed to extend the variety and focus of the psychological interventions that are available. Studies are also needed to explore the longer-term benefits of such interventions.


Assuntos
Psicoterapia/métodos , Dermatopatias/terapia , Adulto , Fatores Etários , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Dermatopatias/psicologia , Resultado do Tratamento
20.
Lupus ; 21(1): 68-74, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22025191

RESUMO

Anti-RNA polymerase III (RNAP III) antibodies are highly specific for scleroderma (SSc) and associated with diffuse SSc and renal crisis. Coexistence of anti-RNAP III and other SSc autoantibodies is rarely documented. We report three cases with coexisting anti-RNAP III and anti-U1RNP. Autoantibodies in 3829 sera from rheumatology clinics were screened by immunoprecipitation. Anti-RNAP III-positive sera were also examined by immunofluorescence and anti-RNAP III ELISA. In total, 35 anti-RNAP III-positive sera were identified by immunoprecipitation, in which three had coexisting anti-U1RNP. All three were anti-RNAP III ELISA positive. Two had anti-RNAP I dominant (vs. RNAP III) reactivity and showed strong nucleolar staining. A case with anti-U1/U2RNP (U2RNP dominant) had systemic lupus erythematosus (SLE)-SSc overlap syndrome; however, the remaining two cases had SLE without signs of SSc. All three cases of anti-RNAP III + U1RNP fulfilled ACR SLE criteria but none in the group with anti-RNAP III alone (p = 0.0002). In contrast, only one case in the former group had sclerodermatous skin changes and Raynaud's phenomenon, vs. 92% with scleroderma in the latter (p < 0.05). Although anti-RNAP III is highly specific for SSc, cases with coexisting anti-U1RNP are not so uncommon among anti-RNAP III positives (8%, 3/35) and may be SLE without features of SSc.


Assuntos
Anticorpos Antinucleares/sangue , Autoanticorpos/sangue , Lúpus Eritematoso Sistêmico , RNA Polimerase III/imunologia , Ribonucleoproteína Nuclear Pequena U1/imunologia , Escleroderma Sistêmico/imunologia , Adulto , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Escleroderma Sistêmico/sangue
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