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1.
Nat Mater ; 22(11): 1311-1316, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37592028

RESUMO

Quantum light emitters capable of generating single photons with circular polarization and non-classical statistics could enable non-reciprocal single-photon devices and deterministic spin-photon interfaces for quantum networks. To date, the emission of such chiral quantum light relies on the application of intense external magnetic fields, electrical/optical injection of spin-polarized carriers/excitons or coupling with complex photonic metastructures. Here we report the creation of free-space chiral quantum light emitters via the nanoindentation of monolayer WSe2/NiPS3 heterostructures at zero external magnetic field. These quantum light emitters emit with a high degree of circular polarization (0.89) and single-photon purity (95%), independent of pump laser polarization. Scanning diamond nitrogen-vacancy microscopy and temperature-dependent magneto-photoluminescence studies reveal that the chiral quantum light emission arises from magnetic proximity interactions between localized excitons in the WSe2 monolayer and the out-of-plane magnetization of defects in the antiferromagnetic order of NiPS3, both of which are co-localized by strain fields associated with the nanoscale indentations.

2.
Phys Rev Lett ; 131(8): 086904, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37683170

RESUMO

We present a comprehensive study of the temperature- and magnetic-field-dependent photoluminescence (PL) of individual NV centers in diamond, spanning the temperature-range from cryogenic to ambient conditions. We directly observe the emergence of the NV's room-temperature effective excited-state structure and provide a clear explanation for a previously poorly understood broad quenching of NV PL at intermediate temperatures around 50 K, as well as the subsequent revival of NV PL. We develop a model based on two-phonon orbital averaging that quantitatively explains all of our findings, including the strong impact that strain has on the temperature dependence of the NV's PL. These results complete our understanding of orbital averaging in the NV excited state and have significant implications for the fundamental understanding of the NV center and its applications in quantum sensing.

3.
Phys Rev Lett ; 128(17): 177401, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35570423

RESUMO

We investigate the magnetic field dependent photophysics of individual nitrogen-vacancy (NV) color centers in diamond under cryogenic conditions. At distinct magnetic fields, we observe significant reductions in the NV photoluminescence rate, which indicate a marked decrease in the optical readout efficiency of the NV's ground state spin. We assign these dips to excited state level anticrossings, which occur at magnetic fields that strongly depend on the effective, local strain environment of the NV center. Our results offer new insights into the structure of the NVs' excited states and a new tool for their effective characterization. Using this tool, we observe strong indications for strain-dependent variations of the NV's orbital g factor, obtain new insights into NV charge state dynamics, and draw important conclusions regarding the applicability of NV centers for low-temperature quantum sensing.

4.
Ophthalmology ; 128(6): 837-847, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33571551

RESUMO

PURPOSE: To examine the association of alcohol consumption and type of alcoholic beverage with incident cataract surgery in 2 large cohorts. DESIGN: Longitudinal, observational study. PARTICIPANTS: We included 469 387 participants of UK Biobank with a mean age of 56 years and 23 162 participants of European Prospective Investigation of Cancer (EPIC)-Norfolk with a mean age of 59 years. METHODS: Self-reported alcohol consumption at baseline was ascertained by a touchscreen questionnaire in UK Biobank and a food-frequency questionnaire in EPIC-Norfolk. Cases were defined as participants undergoing cataract surgery in either eye as ascertained via data linkage to National Health Service procedure statistics. We excluded participants with cataract surgery up to 1 year after the baseline assessment visit or those with self-reported cataract at baseline. Cox proportional hazards models were used to examine the associations of alcohol consumption with incident cataract surgery, adjusted for age, sex, ethnicity, Townsend deprivation index, body mass index (BMI), smoking, and diabetes status. MAIN OUTCOME MEASURES: Incident cataract surgery. RESULTS: There were 19 011 (mean cohort follow-up of 95 months) and 4573 (mean cohort follow-up of 193 months) incident cases of cataract surgery in UK Biobank and EPIC-Norfolk, respectively. Compared with nondrinkers, drinkers were less likely to undergo cataract surgery in UK Biobank (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.85-0.93) and EPIC-Norfolk (HR, 0.90; 95% CI, 0.84-0.97) after adjusting for covariables. Among alcohol consumers, greater alcohol consumption was associated with a reduced risk of undergoing cataract surgery in EPIC-Norfolk (P < 0.001), whereas a U-shaped association was observed in the UK Biobank. Compared with nondrinkers, subgroup analysis by type of alcohol beverage showed the strongest protective association with wine consumption; the risk of incident cataract surgery was 23% and 14% lower among those in the highest category of wine consumption in EPIC-Norfolk and UK Biobank, respectively. CONCLUSIONS: Our findings suggest a lower risk of undergoing cataract surgery with low to moderate alcohol consumption. The association was particularly apparent with wine consumption. We cannot exclude the possibility of residual confounding, and further studies are required to determine whether this association is causal in nature.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Catarata/complicações , Complicações Pós-Operatórias/epidemiologia , Autorrelato , Consumo de Bebidas Alcoólicas/epidemiologia , Catarata/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Fatores de Risco , Reino Unido/epidemiologia
5.
Nano Lett ; 20(3): 1855-1861, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32017577

RESUMO

We realize a cryogenic wide-field nitrogen-vacancy microscope and use it to image Abrikosov vortices and transport currents in a superconducting Nb film. We observe the disappearance of vortices upon increase of laser power and their clustering about hot spots upon decrease, indicating local quenching of superconductivity by the laser. Resistance measurements confirm the presence of large temperature gradients across the film. We then investigate the effect of such gradients on transport currents where the current path is seen to correlate with the temperature profile even in the fully superconducting phase. In addition to highlighting the role of temperature inhomogeneities in superconductivity phenomena, this work establishes that under sufficiently low laser power conditions wide-field nitrogen-vacancy microscopy enables imaging over mesoscopic scales down to 4 K with submicrometer spatial resolution, providing a new platform for spatially resolved investigations of a range of systems from topological insulators to van der Waals ferromagnets.

6.
Clin Exp Ophthalmol ; 46(9): 1041-1047, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29808573

RESUMO

IMPORTANCE: To investigate the safety, effectiveness and follow-up rates after transscleral diode laser cyclophotocoagulation as primary treatment for seeing eyes with primary open angle glaucoma in Bauchi, Nigeria. BACKGROUND: There is a high prevalence of primary open angle glaucoma in Africa where adherence to medical treatment and acceptance of surgery are poor. DESIGN: Prospective case series. PARTICIPANTS: New glaucoma patients where surgical intervention was recommended. METHODS: A diode 810 nm laser G-probe was used under retrobulbar anaesthesia to deliver approximately 20 shots for 2000 ms, titrating the power. If both eyes were treated the first was the study eye. Repeat treatment offered if the intraocular pressure (IOP) was >21 mmHg on two consecutive visits. MAIN OUTCOME MEASURES: IOP < 22 mmHg, change in ≥2 lines of Snellen visual acuity (VA), and complications. RESULTS: 201 out of 204 eyes with complete data analysed. Mean age 52 years, 17 (8.3%) eyes were re-treated. Mean pre-treatment IOP was 39 (SD 11) mmHg. 106 (53%) attended at 12 months when the mean IOP was 19 (7-45) mmHg; 77 (73%) had IOP < 22 mmHg. VAs were better in 13 (12.3%) and worse in 23 (21.7%) eyes. Postoperative complications included mild uveitis (5.5%), corneal oedema (2.5%), severe uveitis (0.5%) and transient hypotony (2.0%). No hypotony at 12 months. CONCLUSIONS AND RELEVANCE: Transscleral diode laser cyclophotocoagulation controlled IOP in almost three quarters of eyes at 12 months with short-term preservation of vision and minimal complications. Poor follow-up in this setting highlights the need for an effective, safe and acceptable treatment where regular follow-up is less critical.


Assuntos
Corpo Ciliar/cirurgia , Glaucoma de Ângulo Aberto/cirurgia , Pressão Intraocular/fisiologia , Fotocoagulação a Laser/métodos , Lasers Semicondutores/uso terapêutico , Esclera/cirurgia , Campos Visuais/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/epidemiologia , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Prevalência , Estudos Prospectivos , Resultado do Tratamento , Acuidade Visual , Adulto Jovem
7.
Sensors (Basel) ; 18(4)2018 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-29690603

RESUMO

Magnetic imaging with ensembles of nitrogen-vacancy (NV) centres in diamond is a recently developed technique that allows for quantitative vector field mapping. Here we uncover a source of artefacts in the measured magnetic field in situations where the magnetic sample is placed in close proximity (a few tens of nm) to the NV sensing layer. Using magnetic nanoparticles as a test sample, we find that the measured field deviates significantly from the calculated field, in shape, amplitude and even in sign. By modelling the full measurement process, we show that these discrepancies are caused by the limited measurement range of NV sensors combined with the finite spatial resolution of the optical readout. We numerically investigate the role of the stand-off distance to identify an artefact-free regime, and discuss an application to ultrathin materials. This work provides a guide to predict and mitigate proximity-induced artefacts that can arise in NV-based wide-field magnetic imaging, and also demonstrates that the sensitivity of these artefacts to the sample can make them a useful tool for magnetic characterisation.

8.
Hum Mol Genet ; 24(13): 3880-92, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25861811

RESUMO

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.


Assuntos
Glaucoma de Ângulo Aberto/genética , Polimorfismo de Nucleotídeo Único , Proteoglicanas/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
9.
Phys Rev Lett ; 118(16): 167204, 2017 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-28474945

RESUMO

The coherent control of spin qubits forms the basis of many applications in quantum information processing and nanoscale sensing, imaging, and spectroscopy. Such control is conventionally achieved by direct driving of the qubit transition with a resonant global field, typically at microwave frequencies. Here we introduce an approach that relies on the resonant driving of nearby environment spins, whose localized magnetic field in turn drives the qubit when the environmental spin Rabi frequency matches the qubit resonance. This concept of environmentally mediated resonance (EMR) is explored experimentally using a qubit based on a single nitrogen-vacancy (NV) center in diamond, with nearby electronic spins serving as the environmental mediators. We demonstrate EMR driven coherent control of the NV spin state, including the observation of Rabi oscillations, free induction decay, and spin echo. This technique also provides a way to probe the nanoscale environment of spin qubits, which we illustrate by acquisition of electron spin resonance spectra from single NV centers in various settings.

10.
Lancet ; 385(9975): 1295-304, 2015 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-25533656

RESUMO

BACKGROUND: Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. METHODS: In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. FINDINGS: We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. INTERPRETATION: This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period. FUNDING: Pfizer, UK National Institute for Health Research Biomedical Research Centre.


Assuntos
Anti-Hipertensivos/administração & dosagem , Glaucoma de Ângulo Aberto/tratamento farmacológico , Prostaglandinas F Sintéticas/administração & dosagem , Administração Oftálmica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Estimativa de Kaplan-Meier , Latanoprosta , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Resultado do Tratamento , Campos Visuais/efeitos dos fármacos , Adulto Jovem
11.
Exp Eye Res ; 143: 28-38, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26432917

RESUMO

There is a growing need for models of human diseases that utilise native, donated human tissue in order to model disease processes and develop novel therapeutic strategies. In this paper we assessed the suitability of adult human retinal explants as a potential model of chronic retinal ganglion cell (RGC) degeneration. Our results confirmed that RGC markers commonly used in rodent studies (NeuN, ßIII Tubulin and Thy-1) were appropriate for labelling human RGCs and followed the expected differential expression patterns across, as well as throughout, the macular and para-macular regions of the retina. Furthermore, we showed that neither donor age nor post-mortem time (within 24 h) significantly affected the initial expression levels of RGC markers. In addition, the feasibility of using human post mortem donor tissue as a long-term model of RGC degeneration was determined with RGC protein being detectable up to 4 weeks in culture with an associated decline in RGC mRNA and significant, progressive, apoptotic labelling of NeuN(+) cells. Differences in RGC apoptosis might have been influenced by medium compositions indicating that media constituents could play a role in supporting axotomised RGCs. We propose that using ex vivo human explants may prove to be a useful model for testing the effectiveness of neuroprotective strategies.


Assuntos
Modelos Teóricos , Degeneração Neural/patologia , Células Ganglionares da Retina/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Nucleares/genética , Apoptose , Biomarcadores/metabolismo , Diferenciação Celular , Sobrevivência Celular , Células Cultivadas , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Marcação In Situ das Extremidades Cortadas , Pessoa de Meia-Idade , Degeneração Neural/metabolismo , Proteínas do Tecido Nervoso/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Células Ganglionares da Retina/metabolismo , Antígenos Thy-1/genética , Doadores de Tecidos , Tubulina (Proteína)/genética
13.
Clin Trials ; 12(6): 608-17, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26183437

RESUMO

BACKGROUND: Understanding the magnitude of non-adherence in pre-marketing clinical trials and clinical practice is essential. However, accurately measuring non-adherence to medication is problematic, and the variety of adherence measures and/or calculation methods has led to highly variable results. PURPOSE: To compare commonly used methods for measuring adherence to eye drop therapy in order to assess which methods achieve the most complete datasets over an 8-month monitoring period, to quantify the magnitude of variance in adherence estimations and to review the different methods used to calculate or interpret adherence data. METHODS: Adherence was measured electronically for 8 months by participants administering eye drops using a Travalert® dosing aid. The mean number of Travalert dosing aid recorded doses administered over the monitoring period was used to calculate a percentage adherence score. In addition, the value of graphically presenting Travalert dosing aid data to classify patterns of adherence behaviour was explored. The validated Morisky Measure of Adherence Scale and questions requesting participants to report the Frequency of Missed Doses were two measures of self-reported adherence calculated for each participant. Finally, medication possession ratio was calculated from expected repeat prescription orders compared with actual repeat prescription orders. RESULTS: For the 208 recruited participants, self-reported adherence was the most reliable method of collecting complete datasets over the 8-month period; 16% of self-reported adherence data were missing compared with 45% of Travalert dosing aid data missing at 8 months. The mean adherence measured over the monitoring period by the Travalert dosing aid was 77%. When adherence measures were dichotomised into adherent and non-adherent groups, the Travalert dosing aid found 54% of participants were adherent, compared to 60% Morisky Measure of Adherence Scale and 57% Frequency of Missed Dose self-report measures. However, there was poor agreement between the Travalert dosing aid measured adherence and self-report measures. Medication possession ratio was not a reliable measure of persistence with medication. Graphical Travalert dosing aid data presentation provided additional information about participant behaviour by indicating that most non-adherence was due to participants taking drug holidays rather than missing occasional doses. CONCLUSION: The analysis provided evidence about the inconsistencies between different monitoring strategies and adherence measures. Furthermore, the analysis highlighted the difficulties in collecting complete data for studies investigating chronic, slowly progressive conditions that require long-term follow-up. Future adherence studies could use multiple methods for quantifying and classifying adherence in parallel, both to maximise precision of adherence estimates and to facilitate comparison between studies. However, the authors are cautious of the effect of using multiple adherence measures on participant behaviour and their potential reactivity effects is an area for future research.


Assuntos
Glaucoma/tratamento farmacológico , Adesão à Medicação , Soluções Oftálmicas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Projetos de Pesquisa , Reino Unido
14.
Public Health ; 129(2): 103-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25687711

RESUMO

OBJECTIVES: To investigate the relationship between area deprivation, individual socio-economic status (SES) and age related macular degeneration (AMD). STUDY DESIGN: Cross sectional study nested within a longitudinal cohort study. METHODS: Data were collected in the EPIC-Norfolk Eye Study by trained nurses, using standardized protocols and lifestyle questionnaires. The English Index of multiple deprivation 2010 (IMD) was derived from participants' postcodes. AMD was identified from standardized grading of fundus photographs. Logistic regression was used to examine associations between IMD, SES and AMD. RESULTS: 5344 pairs (62.0% of total 8623) of fundus photographs were of sufficient quality for grading of AMD. Of 5182 participants with complete data, AMD was identified in 653 participants (12.60%, 95%CI = 11.7-13.5%). Multivariable logistic regression showed that people living in the most affluent 5% of areas had nearly half the odds of AMD compared to those living in comparatively more deprived areas (OR = 0.56, 95% CI = 0.36-0.89, P = 0.02), after adjusting for age, sex, education, social class and smoking. CONCLUSIONS: The authors found that living in the most affluent areas exerted a protective effect on AMD, independently of education and social class. Further investigation into underlying mechanisms will inform potential interventions to reduce health inequalities relating to AMD.


Assuntos
Disparidades nos Níveis de Saúde , Degeneração Macular/epidemiologia , Áreas de Pobreza , Classe Social , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Estilo de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Fumar/epidemiologia , Inquéritos e Questionários , Reino Unido/epidemiologia
15.
Aesthet Surg J ; 35 Suppl 1: S3-10, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25948657

RESUMO

BACKGROUND: On March 9, 2012, the Food and Drug Administration (FDA) approved Sientra's premarket approval application for its portfolio of silicone gel breast implants based on their review of Sientra's 3-year study data from the largest pivotal silicone gel breast implant study to date. This included the first approval of shaped breast implants in the United States. OBJECTIVES: The authors provide an update to the 8-year safety and effectiveness of the Sientra High-Strength silicone gel breast implants. METHODS: The Sientra Core study is an ongoing 10 year open-label, prospective, multi-center clinical study, which includes 1788 patients implanted with 3506 Sientra implants across four indications (Primary Augmentation, Revision Augmentation, Primary Reconstruction, and Revision Reconstruction). For the safety analysis, the incidence of post-operative complications, including all breast implant-related adverse effects (eg, infection, asymmetry), was estimated based on Kaplan-Meier risk rates. The effectiveness analyses include surgeon and patient satisfaction and changes in bra/cup size. RESULTS: Through 8 years, the overall risk of rupture was 4.6%, the risk of capsular contracture was 11.8% (rates were lower when using True Texture™), and the risk of reoperation was 28.3%. Out of the 580 reoperations in 456 patients, over half of all reoperations were due to cosmetic reasons (n = 299). The most common reasons for reoperation were capsular contracture (19.0%), style and/or size change (18.4%), and asymmetry (8.8%). Patient satisfaction remains high through 8 years, with 87% indicating that their breast implants make them feel more feminine than prior to enrollment. CONCLUSIONS: Safety data from the FDA Core study continues to support a comprehensive safety and effectiveness profile of Sientra's portfolio of round and shaped implants through 8 years. LEVEL OF EVIDENCE: 3 Therapeutic.


Assuntos
Implante Mamário , Implantes de Mama , Adolescente , Adulto , Idoso , Implantes de Mama/efeitos adversos , Feminino , Seguimentos , Humanos , Contratura Capsular em Implantes/epidemiologia , Contratura Capsular em Implantes/cirurgia , Pessoa de Meia-Idade , Satisfação do Paciente , Desenho de Prótese , Falha de Prótese , Reoperação/estatística & dados numéricos , Ruptura , Géis de Silicone , Estados Unidos/epidemiologia , Adulto Jovem
16.
Hum Mol Genet ; 21(4): 852-62, 2012 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22062891

RESUMO

Myotonic dystrophy (DM) is caused by a triplet repeat expansion in the non-coding region of either the DMPK (DM1) or CNBP (DM2) gene. Transcription of the expanded region causes accumulation of double-stranded RNA (dsRNA) in DM cells. We sought to determine how expression of triplet repeat RNA causes the varied phenotype typical of DM. Global transcription was measured in DM and non-DM cataract samples using Illumina Bead Arrays. DM samples were compared with non-DM samples and lists of differentially expressed genes (P≤ 0.05) were prepared. Gene set enrichment analysis and the Interferome database were used to search for significant patterns of gene expression in DM cells. Expression of individual genes was measured using quantitative real-time polymerase chain reaction. DMPK and CNBP expression was confirmed in native lens cells showing that a toxic RNA gain of function mechanism could exist in lens. A high proportion, 83% in DM1 and 75% in DM2, of the significantly disregulated genes were shared by both forms of the disease, suggesting a common mechanism. The upregulated genes in DM1 and DM2 were highly enriched in both interferon-regulated genes (IRGs) and genes associated with the response to dsRNA and the innate immune response. The characteristic fingerprint of IRGs and the signalling pathways identified in lens cells support a role for dsRNA activation of the innate immune response in the pathology of DM. This new evidence forms the basis for a novel hypothesis to explain the complex mechanism of DM.


Assuntos
Catarata/genética , Imunidade Inata/imunologia , Interferons/metabolismo , Transtornos Miotônicos/complicações , Distrofia Miotônica/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Catarata/etiologia , Catarata/imunologia , Catarata/patologia , Células Epiteliais/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Humanos , Interferons/imunologia , Cristalino/patologia , Masculino , Pessoa de Meia-Idade , Transtornos Miotônicos/genética , Distrofia Miotônica/genética , Miotonina Proteína Quinase , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais , Transcriptoma/genética
17.
Ophthalmology ; 121(8): 1501-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24702754

RESUMO

OBJECTIVE: To determine the association between systemic medication use and intraocular pressure (IOP) in a population of older British men and women. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: We included 7093 participants from the European Prospective Investigation into Cancer-Norfolk Eye Study. Exclusion criteria were a history of glaucoma therapy (medical, laser, or surgical), IOP asymmetry between eyes of >5 mmHg, and missing data for any covariables. The mean age of participants was 68 years (range, 48-92) and 56% were women. METHODS: We measured IOP using the Ocular Response Analyzer. Three readings were taken per eye and the best signal value of the Goldmann-correlated IOP value considered. Participants were asked to bring all their medications and related documentation to the health examination, and these were recorded by the research nurse using an electronic case record form. The medication classes examined were angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, α-blockers, ß-blockers, calcium channel blockers, diuretics, nitrates, statins, insulin, biguanides, sulfonylureas, aspirin, and other nonsteroidal anti-inflammatory drugs. We examined associations between medication use and IOP using multivariable linear regression models adjusted for age, sex, and body mass index. Models containing diabetic medication were further adjusted for glycosylated hemoglobin levels. MAIN OUTCOME MEASURES: Mean IOP of the right and left eyes. RESULTS: Use of systemic ß-blockers (-0.92 mmHg; 95% CI, -1.19, -0.65; P<0.001) and nitrates (-0.63 mmHg; 95% CI, -1.12, -0.14; P = 0.011) were independently associated with lower IOP. The observed associations between statin or aspirin use with IOP were no longer significant after adjustment for ß-blocker use. CONCLUSIONS: This is the first population-based study to demonstrate and quantify clinically significant differences in IOP among participants using systemic ß-blockers or nitrates. Lower IOP observed in participants using statins or aspirin was explained by concurrent systemic ß-blocker use. The study findings may have implications for the management of glaucoma patients with comorbidity, and may provide insight into the pathophysiologic processes underlying IOP.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Aspirina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pressão Intraocular/efeitos dos fármacos , Nitratos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biguanidas/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Estudos Transversais , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/induzido quimicamente , Hipertensão Ocular/prevenção & controle , Estudos Prospectivos , Compostos de Sulfonilureia/efeitos adversos , Tonometria Ocular , Reino Unido
18.
BMC Ophthalmol ; 14: 32, 2014 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-24655814

RESUMO

BACKGROUND: Improving adherence to ocular hypertension (OH)/glaucoma therapy is highly likely to prevent or reduce progression of optic nerve damage. The present study used a behaviour change counselling intervention to determine whether education and support was beneficial and cost-effective in improving adherence with glaucoma therapy. METHODS: A randomised controlled trial with a 13-month recruitment and 8-month follow-up period was conducted. Patients with OH/glaucoma attending a glaucoma clinic and starting treatment with travoprost were approached. Participants were randomised into two groups and adherence was measured over 8 months, using an electronic monitoring device (Travalert® dosing aid, TDA). The control group received standard clinical care, and the intervention group received a novel glaucoma education and motivational support package using behaviour change counselling. Cost-effectiveness framework analysis was used to estimate any potential cost benefit of improving adherence. RESULTS: Two hundred and eight patients were recruited (102 intervention, 106 control). No significant difference in mean adherence over the monitoring period was identified with 77.2% (CI, 73.0, 81.4) for the control group and 74.8% (CI, 69.7, 79.9) for the intervention group (p = 0.47). Similarly, there was no significant difference in percentage intraocular pressure reduction; 27.6% (CI, 23.5, 31.7) for the control group and 25.3% (CI, 21.06, 29.54) for the intervention group (p = 0.45). Participants in the intervention group were more satisfied with information about glaucoma medication with a mean score of 14.47/17 (CI, 13.85, 15.0) compared with control group which was 8.51 (CI, 7.72, 9.30). The mean intervention cost per patient was GB£10.35 (

Assuntos
Anti-Hipertensivos/uso terapêutico , Cloprostenol/análogos & derivados , Glaucoma/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Hipertensão Ocular/tratamento farmacológico , Educação de Pacientes como Assunto , Assistência Centrada no Paciente/métodos , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Cloprostenol/uso terapêutico , Aconselhamento/métodos , Feminino , Custos de Cuidados de Saúde , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/economia , Educação de Pacientes como Assunto/métodos , Educação de Pacientes como Assunto/normas , Satisfação do Paciente , Travoprost
19.
Community Eye Health ; 32(107): 58-59, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32123478
20.
Nat Commun ; 15(1): 8059, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277615

RESUMO

Josephson junctions enable dissipation-less electrical current through metals and insulators below a critical current. Despite being central to quantum technology based on superconducting quantum bits and fundamental research into self-conjugate quasiparticles, the spatial distribution of super current flow at the junction and its predicted evolution with current bias and external magnetic field remain experimentally elusive. Revealing the hidden current flow, featureless in electrical resistance, helps understanding unconventional phenomena such as the nonreciprocal critical current, i.e., Josephson diode effect. Here we introduce a platform to visualize super current flow at the nanoscale. Utilizing a scanning magnetometer based on nitrogen vacancy centers in diamond, we uncover competing ground states electrically switchable within the zero-resistance regime. The competition results from the superconducting phase re-configuration induced by the Josephson current and kinetic inductance of thin-film superconductors. We further identify a new mechanism for the Josephson diode effect involving the Josephson current-induced phase. The nanoscale super current flow emerges as a new experimental observable for elucidating unconventional superconductivity, and optimizing quantum computation and energy-efficient devices.

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