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1.
J Clin Virol ; 171: 105654, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38387136

RESUMO

BACKGROUND: The advent of lateral flow devices (LFDs) for SARS-CoV-2 detection enabled widespread use of rapid self-tests during the pandemic. While self-testing using LFDs is now common, whether self-testing provides comparable performance to professional testing was a key question that remained important for pandemic planning. METHODS: Three prospective multi-centre studies were conducted to compare the performance of self- and professional testing using LFDs. Participants tested themselves or were tested by trained (professional) testers at community testing sites in the UK. Corresponding qRT-PCR test results served as reference standard. The performance of Innova, Orient Gene and SureScreen LFDs by users (self) and professional testers was assessed in terms of sensitivity, specificity, and kit failure (void) rates. Impact of age, sex and symptom status was analysed using logistic regression modelling. RESULTS: 16,617 participants provided paired tests, of which 15,418 were included in the analysis. Self-testing with Innova, Orient Gene or SureScreen LFDs achieved sensitivities of 50 %, 53 % or 72 %, respectively, compared to qRT-PCR. Self and professional LFD testing showed no statistically different sensitivity with respect to corresponding qRT-PCR testing. Specificity was consistently equal to or higher than 99 %. Sex and age had no or only marginal impact on LFD performance while sensitivity was significantly higher for symptomatic individuals. Sensitivity of LFDs increased strongly to up to 90 % with higher levels of viral RNA measured by qRT-PCR. CONCLUSIONS: Our results support SARS-CoV-2 self-testing with LFDs, especially for the detection of individuals whose qRT-PCR tests showed high viral concentrations.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , Estudos Prospectivos , SARS-CoV-2 , Testes Imunológicos , Reino Unido , Sensibilidade e Especificidade
2.
Philos Trans R Soc Lond B Biol Sci ; 378(1890): 20220243, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37778382

RESUMO

Post-translational modifications (PTMs) of proteins are central to epigenetic regulation and cellular signalling, playing an important role in the pathogenesis and progression of numerous diseases. Growing evidence indicates that protein arginine citrullination, catalysed by peptidylarginine deiminases (PADs), is involved in many aspects of molecular and cell biology and is emerging as a potential druggable target in multiple diseases including cancer. However, we are only just beginning to understand the molecular activities of PADs, and their underlying mechanistic details in vivo under both physiological and pathological conditions. Many questions still remain regarding the dynamic cellular functions of citrullination and its interplay with other types of PTMs. This review, therefore, discusses the known functions of PADs with a focus on cancer biology, highlighting the cross-talk between citrullination and other types of PTMs, and how this interplay regulates downstream biological events. This article is part of the Theo Murphy meeting issue 'The virtues and vices of protein citrullination'.


Assuntos
Citrulinação , Neoplasias , Humanos , Hidrolases/metabolismo , Epigênese Genética , Proteínas/metabolismo , Desiminases de Arginina em Proteínas/metabolismo , Processamento de Proteína Pós-Traducional
3.
Nat Commun ; 14(1): 1078, 2023 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-36841868

RESUMO

Protein arginine methyltransferase (PRMT) 5 is over-expressed in a variety of cancers and the master transcription regulator E2F1 is an important methylation target. We have explored the role of PRMT5 and E2F1 in regulating the non-coding genome and report here a striking effect on long non-coding (lnc) RNA gene expression. Moreover, many MHC class I protein-associated peptides were derived from small open reading frames in the lncRNA genes. Pharmacological inhibition of PRMT5 or adjusting E2F1 levels qualitatively altered the repertoire of lncRNA-derived peptide antigens displayed by tumour cells. When presented to the immune system as either ex vivo-loaded dendritic cells or expressed from a viral vector, lncRNA-derived peptides drove a potent antigen-specific CD8 T lymphocyte response, which translated into a significant delay in tumour growth. Thus, lncRNA genes encode immunogenic peptides that can be deployed as a cancer vaccine.


Assuntos
Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Neoplasias/genética , Neoplasias/terapia , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Peptídeos/genética , Linfócitos T CD8-Positivos , Proteína-Arginina N-Metiltransferases
4.
Sci Rep ; 11(1): 14012, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234234

RESUMO

Natural sediment flocs are fragile, highly irregular, loosely bound aggregates comprising minerogenic and organic material. They contribute a major component of suspended sediment load and are critical for the fate and flux of sediment, carbon and pollutants in aquatic environments. Understanding their behaviour is essential to the sustainable management of waterways, fisheries and marine industries. For several decades, modelling approaches have utilised fractal mathematics and observations of two dimensional (2D) floc size distributions to infer levels of aggregation and predict their behaviour. Whilst this is a computationally simple solution, it is highly unlikely to reflect the complexity of natural sediment flocs and current models predicting fine sediment hydrodynamics are not efficient. Here, we show how new observations of fragile floc structures in three dimensions (3D) demonstrate unequivocally that natural flocs are non-fractal. We propose that floc hierarchy is based on observations of 3D structure and function rather than 2D size distribution. In contrast to fractal theory, our data indicate that flocs possess characteristics of emergent systems including non-linearity and scale-dependent feedbacks. These concepts and new data to quantify floc structures offer the opportunity to explore new emergence-based floc frameworks which better represent natural floc behaviour and could advance our predictive capacity.

5.
Int J Audiol ; 60(7): 549-554, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33336606

RESUMO

OBJECTIVE: Auditory brainstem response (ABR) is used to determine hearing thresholds in children who cannot undergo behavioural testing. Children must remain still during testing, with general anaesthesia (GA) in theatre required for those who cannot. We developed a protocol whereby an ABR was undertaken in a ward environment using only intranasal dexmedetomidine for sedation. DESIGN: Prospective data were collected including the time of sedation onset, ABR duration and arrival to discharge time was recorded and feedback was requested using a questionnaire. STUDY SAMPLE: Twenty-nine consecutive patients routinely undergoing an ABR. RESULTS: From this pilot study, we demonstrated that intranasal dexmedetomidine could be used successfully to administer safe sedation to all twenty-nine children undergoing an ABR in a ward environment as opposed to theatre. CONCLUSIONS: This allowed for faster time to discharge compared to GA, produced what was felt to be a better quality ABR trace, better utilization of a theatre slot, negated the need for GA in a child and created a less stressful experience for both parent and child according to information from feedback questionnaires.


Assuntos
Dexmedetomidina , Criança , Dexmedetomidina/efeitos adversos , Potenciais Evocados Auditivos do Tronco Encefálico , Humanos , Hipnóticos e Sedativos/efeitos adversos , Lactente , Projetos Piloto , Estudos Prospectivos
6.
Cell Death Dis ; 11(7): 572, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32709847

RESUMO

The pRb-E2F pathway is a critical point of regulation in the cell cycle and loss of control of the pathway is a hallmark of cancer. E2F1 is the major target through which pRb exerts its effects and arginine methylation by PRMT5 plays a key role in dictating E2F1 activity. Here we have explored the functional role of the PRMT5-E2F1 axis and highlight its influence on different aspects of cancer cell biology including viability, migration, invasion and adherence. Through a genome-wide expression analysis, we identified a distinct set of genes under the control of PRMT5 and E2F1, including some highly regulated genes, which influence cell migration, invasio and adherence through a PRMT5-dependent mechanism. Most significantly, a coincidence was apparent between the expression of PRMT5 and E2F1 in human tumours, and elevated levels of PRMT5 and E2F1 correlated with poor prognosis disease. Our results suggest a causal relationship between PRMT5 and E2F1 in driving the malignant phenotype and thereby highlight an important pathway for therapeutic intervention.


Assuntos
Movimento Celular , Fator de Transcrição E2F1/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Proteína-Arginina N-Metiltransferases/metabolismo , Transdução de Sinais , Linhagem Celular Tumoral , Movimento Celular/genética , Cortactina/genética , Cortactina/metabolismo , Regulação para Baixo/genética , Fator de Transcrição E2F1/genética , Adesões Focais/metabolismo , Regulação Neoplásica da Expressão Gênica , Genoma Humano , Humanos , Invasividade Neoplásica , Neoplasias/genética , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Proteína-Arginina N-Metiltransferases/genética , Transdução de Sinais/genética
7.
Otol Neurotol ; 41(7): e864-e872, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32569143

RESUMO

OBJECTIVE: To review insights gained from a 21-year experience with gentamicin-induced vestibulotoxicity including differences in vestibulotoxicity between single daily dosing (SDD) and multiple daily dosing (MDD) regimens. STUDY DESIGN: Retrospective case series. SETTING: Tertiary care center. PATIENTS: Patients with gentamicin vestibulotoxicity referred to the Hertz Multidisciplinary Neurotology Clinic between January 1993 and September 2014. INTERVENTION: None. MAIN OUTCOME MEASURES: Spectrum of vestibular dysfunction measured using videonystagmography, vestibular evoked myogenic potentials, video head impulse testing, and magnetic scleral search coil testing. RESULTS: Of 53 patients with gentamicin-induced vestibulotoxicity, 24 received SDD and 29 received MDD treatment. The most common indications for treatment were sepsis, endocarditis, and osteomyelitis. Angular acceleration receptor function (semicircular canals) was more commonly affected than linear acceleration receptor function (otolithic organ of the saccule; 100% vs. 62%). A significant proportion of patients (53%) developed vestibulotoxicity in the absence of nephrotoxicity and 40% experienced vestibulotoxicity in a delayed fashion up to 10 days posttreatment cessation (mean 3.9 ±â€Š0.7). Therapeutic monitoring did not necessarily prevent delayed vestibulotoxicity. Nephrotoxicity was less common for SDD compared with MDD (60% vs. 35%, p = 0.01). However, the SDD group experienced vestibulotoxicity at a lower cumulative dose (6.3 vs. 7.0 g, p = 0.04) and shorter duration of therapy (20.7 vs 29.4 d, p = 0.02). CONCLUSIONS: Our study further highlights important insights regarding gentamicin-induced vestibulotoxicity. While SDD is associated with decreased risk for nephrotoxicity compared with MDD, it confers a higher risk for vestibulotoxicity.


Assuntos
Gentamicinas , Potenciais Evocados Miogênicos Vestibulares , Gentamicinas/efeitos adversos , Humanos , Estudos Retrospectivos , Sáculo e Utrículo , Canais Semicirculares
8.
J Int Adv Otol ; 16(1): 127-129, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32401208

RESUMO

We present an unusual case of a patient with a positive Tullio phenomenon, brief Valsalva-induced transient horizontal nystagmus, reduced left caloric response, and bilateral vestibulo-ocular reflex loss. This study discusses the pathophysiology and differential diagnosis concerning the suspected pathology for the phenomenon of utricular hydrops or vestibular atelectasis and presents a literature review.


Assuntos
Nistagmo Patológico/etiologia , Vertigem/etiologia , Vestíbulo do Labirinto/fisiopatologia , Diagnóstico Diferencial , Edema/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Ruído/efeitos adversos , Nistagmo Patológico/diagnóstico , Nistagmo Patológico/fisiopatologia , Pressão/efeitos adversos , Atelectasia Pulmonar/diagnóstico , Reflexo Vestíbulo-Ocular/fisiologia , Sáculo e Utrículo/patologia , Osso Temporal/diagnóstico por imagem , Vertigem/diagnóstico , Vertigem/fisiopatologia , Potenciais Evocados Miogênicos Vestibulares/fisiologia , Testes de Função Vestibular/métodos , Vestíbulo do Labirinto/patologia
9.
Sci Adv ; 5(6): eaaw4640, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31249870

RESUMO

E2F is a family of master transcription regulators involved in mediating diverse cell fates. Here, we show that residue-specific arginine methylation (meR) by PRMT5 enables E2F1 to regulate many genes at the level of alternative RNA splicing, rather than through its classical transcription-based mechanism. The p100/TSN tudor domain protein reads the meR mark on chromatin-bound E2F1, allowing snRNA components of the splicing machinery to assemble with E2F1. A large set of RNAs including spliced variants associate with E2F1 by virtue of the methyl mark. By focusing on the deSUMOylase SENP7 gene, which we identified as an E2F target gene, we establish that alternative splicing is functionally important for E2F1 activity. Our results reveal an unexpected consequence of arginine methylation, where reader-writer interplay widens the mechanism of control by E2F1, from transcription factor to regulator of alternative RNA splicing, thereby extending the genomic landscape under E2F1 control.


Assuntos
Arginina/genética , Fatores de Transcrição E2F/genética , Processamento Alternativo/genética , Linhagem Celular , Cromatina/genética , Endopeptidases/genética , Genômica , Humanos , Metilação , RNA/genética
10.
Sci Total Environ ; 660: 1419-1432, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30743935

RESUMO

Managed realignment (MR) schemes are being implemented to compensate for the loss of intertidal saltmarsh habitats by breaching flood defences and inundating the formerly defended coastal hinterland. However, studies have shown that MR sites have lower biodiversity than anticipated, which has been linked with anoxia and poor drainage resulting from compaction and the collapse of sediment pore space caused by the site's former terrestrial land use. Despite this proposed link between biodiversity and soil structure, the evolution of the sediment sub-surface following site inundation has rarely been examined, particularly over the early stages of the terrestrial to marine or estuarine transition. This paper presents a novel combination of broad- and intensive-scale analysis of the sub-surface evolution of the Medmerry Managed Realignment Site (West Sussex, UK) in the three years following site inundation. Repeated broad-scale sediment physiochemical datasets are analysed to assess the early changes in the sediment subsurface and the preservation of the former terrestrial surface, comparing four locations of different former land uses. Additionally, for two of these locations, high-intensity 3D-computed X-ray microtomography and Itrax micro-X-ray fluorescence spectrometry analyses are presented. Results provide new data on differences in sediment properties and structure related to the former land use, indicating that increased agricultural activity leads to increased compaction and reduced porosity. The presence of anoxic conditions, indicative of poor hydrological connectivity between the terrestrial and post-inundation intertidal sediment facies, was only detected at one site. This site has experienced the highest rate of accretion over the terrestrial surface (ca. 7 cm over 36 months), suggesting that poor drainage is caused by the interaction (or lack of) between sediment facies rather than the former land use. This has significant implications for the design of future MR sites in terms of preparing sites, their anticipated evolution, and the delivery of ecosystem services.

11.
Otol Neurotol ; 39(8): 1031-1036, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29912834

RESUMO

INTRODUCTION: Bilateral posterior semicircular canal (PSCC) occlusion is a successful treatment of bilateral benign positional vertigo (BPV) refractory to particle repositioning manoeuvers. Little about the effects on the vestibular ocular reflex (VOR) postoperatively, which is the intent of this study. METHODS: All patients who underwent bilateral posterior canal occlusion for BPV at the University Health Network by the senior author (J.A.R.) between 2001 and 2017 with pre- and postoperative vestibular testing were included in the study.All patients underwent a detailed history and neuro-otological examination including dynamic visual acuity (DVA). Laboratory testing including video head impulse testing or magnetic scleral search coil testing, video nystagmography, cervical and ocular vestibular evoked myogenic potentials and audiological testing before and following their procedure at 1, 6, and 12 months postoperatively. RESULTS: Three patients were included in the study, all females, with a mean age of 41 years (range 36-44 yr). All patients had developed bilateral BPV after head trauma. Mean length of follow-up was 26 months (range 6-84 mo). All patients demonstrated a reduction in the vertical VOR of between 0.37 and 0.57/s at 1 month postocclusion. Between 6 and 12 months postoperatively, an improvement in their vertical VOR between 0.45 and 0.75/s was observed. Clinically, all patients reported complete resolution of their positional vertigo with a negative Dix-Hallpike bilaterally at follow-up. None reported oscillopsia, which was confirmed with DVA testing. CONCLUSION: Bilateral PSCC occlusion results in a reduction in the vertical VOR of the PSCCs.Over a 6 to 12 month time period improvement in the VOR gain can be demonstrated, most likely due to central compensation. There is clinical correlation with improvement in DVA testing. Bilateral PSCC occlusion is a safe and effective treatment for bilateral BPV proved refractory to particle repositioning manoeuvers.


Assuntos
Vertigem Posicional Paroxística Benigna/cirurgia , Canais Semicirculares/cirurgia , Vestíbulo do Labirinto/cirurgia , Adulto , Vertigem Posicional Paroxística Benigna/diagnóstico , Feminino , Teste do Impulso da Cabeça , Humanos , Reflexo Vestíbulo-Ocular , Resultado do Tratamento , Potenciais Evocados Miogênicos Vestibulares/fisiologia
12.
BMC Health Serv Res ; 18(1): 110, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29433479

RESUMO

BACKGROUND: Tinnitus service provision in the United Kingdom has been investigated from the healthcare provider's perspective demonstrating considerable regional variation particularly regarding availability of psychological treatments. An audiological-based tinnitus service, however, was reportedly available for all tinnitus patients in the UK. The aim of the current study was to define and evaluate nationwide tinnitus healthcare services from the patients' viewpoint. METHODS: Secondary analyses were performed on data from a 33-item questionnaire provided by the British Tinnitus Association. The questionnaire had been distributed via email and social media. RESULTS: Responses from 937 participants who had or had previously experienced tinnitus were analysed. All but one person had at some time consulted their GP. About one in five received medication in primary care. The majority were referred to secondary care, generally an ENT surgeon or audiovestibular physician; some were referred directly to audiological services. In secondary care the majority underwent audiometric testing and over half underwent MRI scanning. Drugs were prescribed less frequently in secondary care. About one third of patients were referred onwards from diagnostic services in secondary care to receive therapeutic interventions for tinnitus. Therapy was generally delivered by an audiologist or hearing therapist. Just under two fifths of people discharged from secondary care returned to their GP, with most returning within one year. Over a third of this group were re-referred to secondary care. Few patients saw a psychologist (2.6%) though some psychological treatments were delivered by appropriately trained audiologists. Negative counselling from healthcare professionals in both primary and secondary care settings was reported. CONCLUSIONS: Although the UK has developed a national service for patients with tinnitus many people find it difficult to access, being blocked at the primary care level or after secondary care diagnostic services. Many of those discharged from secondary care return to their GP within a short space of time and are re-referred to secondary care creating an unsatisfactory and expensive revolving-door pattern of healthcare. Despite psychological treatment modalities having the best evidence base for successful tinnitus management, only a minority of tinnitus patients ever get to meet a psychologist.


Assuntos
Satisfação do Paciente , Zumbido/terapia , Idoso , Aconselhamento , Feminino , Pesquisas sobre Atenção à Saúde , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde , Encaminhamento e Consulta , Atenção Secundária à Saúde , Reino Unido
13.
Cell Death Differ ; 24(12): 2139-2149, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28841214

RESUMO

The retinoblastoma tumour suppressor protein (pRb) classically functions to regulate early cell cycle progression where it acts to enforce a number of checkpoints in response to cellular stress and DNA damage. Methylation at lysine (K) 810, which occurs within a critical CDK phosphorylation site and antagonises a CDK-dependent phosphorylation event at the neighbouring S807 residue, acts to hold pRb in the hypo-phosphorylated growth-suppressing state. This is mediated in part by the recruitment of the reader protein 53BP1 to di-methylated K810, which allows pRb activity to be effectively integrated with the DNA damage response. Here, we report the surprising observation that an additional methylation-dependent interaction occurs at K810, but rather than the di-methyl mark, it is selective for the mono-methyl K810 mark. Binding of the mono-methyl PHF20L1 reader to methylated pRb occurs on E2F target genes, where it acts to mediate an additional level of control by recruiting the MOF acetyltransferase complex to E2F target genes. Significantly, we find that the interplay between PHF20L1 and mono-methyl pRb is important for maintaining the integrity of a pRb-dependent G1-S-phase checkpoint. Our results highlight the distinct roles that methyl-lysine readers have in regulating the biological activity of pRb.


Assuntos
Proteínas Cromossômicas não Histona/metabolismo , Lisina/metabolismo , Proteína do Retinoblastoma/metabolismo , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Proteínas Cromossômicas não Histona/genética , Genes Supressores de Tumor , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Humanos , Células MCF-7 , Metilação , Proteína do Retinoblastoma/genética , Transfecção , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/genética , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo
14.
Cell Rep ; 19(11): 2193-2201, 2017 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-28614707

RESUMO

The retinoblastoma tumor suppressor protein pRb is a master regulator of cellular proliferation, principally through interaction with E2F and regulation of E2F target genes. Here, we describe the H1.2 linker histone as a major pRb interaction partner. We establish that H1.2 and pRb are found in a chromatin-bound complex on diverse E2F target genes. Interrogating the global influence of H1.2 on the genome-wide distribution of pRb indicated that the E2F target genes affected by H1.2 are functionally linked to cell-cycle control, consistent with the ability of H1.2 to hinder cell proliferation and the elevated levels of chromatin-bound H1-pRb complex, which occur in growth-arrested cells. Our results define a network of E2F target genes as susceptible to the regulatory influence of H1.2, where H1.2 augments global association of pRb with chromatin, enhances transcriptional repression by pRb, and facilitates pRb-dependent cell-cycle arrest.


Assuntos
Cromatina/genética , Genes Supressores de Tumor/fisiologia , Histonas/genética , Proteína do Retinoblastoma/metabolismo , Retinoblastoma/genética , Pontos de Checagem do Ciclo Celular , Humanos , Transfecção
15.
Cochlear Implants Int ; 18(3): 180-185, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28274186

RESUMO

OBJECTIVES: Cochlear implantation (CI) under local anaesthetic (LA) has previously been shown to be a successful and safe option for a specific group of patients (e.g. elderly and significant co-morbidity). We aim to discuss our practice and obtain qualitative information about patient experience from our cohort of patients at the Yorkshire Auditory Implant Service (YAIS). METHODS: Retrospective chart review to include demographics, co-morbidities and physiological parameters were recorded and used to calculate P-POSSUM (Portsmouth Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity) scores. The Iowa Satisfaction with Anaesthesia Scale (ISAS) questionnaire was distributed to all patients who received CI under LA and subsequently analysed. RESULTS: Seven patients received CI under LA at YAIS. This included five males and two females. The mean age was 79 years (range 26 -93). The mean P-POSSUM mortality and morbidity for this cohort was 2.4 and 34.9%, respectively. The average ISAS score was +1.72 (where range of -3 is completely dissatisfied and +3 is completely satisfied). DISCUSSION: We discuss our cohort and show that patients receiving CI have a favourable experience when LA is used. CI under LA is a viable and safe option for more elderly patients and those who are deemed at high risk of morbidity or mortality associated with a general anaesthetic. CONCLUSIONS: The data regarding validated patient experience obtained from this study can be used to help counsel patients that may be offered CI under LA.


Assuntos
Anestesia Local/psicologia , Anestésicos Locais , Implante Coclear/psicologia , Satisfação do Paciente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Local/métodos , Implante Coclear/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento
16.
Sci Total Environ ; 587-588: 47-58, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28215810

RESUMO

Saltmarshes are being lost or degraded as a result of human activity resulting in loss of critical ecosystem services including the provision of wild species diversity, water quality regulation and flood regulation. To compensate, saltmarshes are being restored or re-created, usually driven by legislative requirements for increased habitat diversity, flood regulation and sustainable coastal defense. Yet, there is increasing evidence that restoration may not deliver anticipated ecosystem services; this is frequently attributed to poor drainage and sediment anoxia. However, physical sediment characteristics, hydrology and the sediment geochemical environment are rarely examined in restoration schemes, despite such factors being critical for plant succession. This study presents the novel integration of 3D-computed X-ray microtomography to quantify sediment structure and porosity, with water level and geochemical data to understand the impact of pre-restoration land use and disturbance on the structure and functioning of restored saltmarshes. The study combines a broad-scale investigation of physical sediment characteristics in nine de-embanked saltmarshes across SE England, with an intensive study at one site examining water levels, sediment structure and the sediment geochemical environment. De-embankment does not restore the hydrological regime, or the physical/chemical framework in the saltmarshes and evidence of disturbance includes a reduction in microporosity, pore connectivity and water storage capacity, a lack of connectivity between the sub-surface environment and overlying floodwaters, and impeded sub-surface water flow and drainage. This has significant consequences for the sediment geochemical environment. This disturbance is evident for at least two decades following restoration and is likely to be irreversible. It has important implications for plant establishment in particular, ecosystem services including flood regulation, nutrient cycling and wild species diversity and for future restoration design.

17.
Pituitary ; 20(4): 395-402, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28154960

RESUMO

INTRODUCTION: In order to perform trans-sphenoidal endoscopic pituitary surgery safely and efficiently it is important to identify anatomical and pituitary disease features on the pre-operative CT and MRI scans; thereby minimising the risk to surrounding structures and optimising outcomes. We aim to create a checklist to streamline pre-operative planning. METHODS: We retrospectively reviewed pre-operative CT and MRI scans of 100 adults undergoing trans-sphenoidal endoscopic pituitary surgery. RESULTS: Radiological findings and their incidence included deviated nasal septum (62%), concha bullosa (32%), bony dehiscence of the carotid arteries (18%), sphenoid septation overlying the internal carotid artery (24% at the sella) and low lying CSF (32%). The mean distance of the sphenoid ostium to the skull base was 10 mm (range 2.7-17.6 mm). We also describe the 'teddy bear' sign which when present on an axial CT indicates the carotid arteries will be identifiable intra-operatively. CONCLUSIONS: There are significant variations in the anatomical and pituitary disease features between patients. We describe a number of features on pre-operative scans and have devised a checklist including a new 'teddy bear' sign to aid the surgeon in the anatomical assessment of patients undergoing trans-sphenoidal pituitary surgery.


Assuntos
Hipófise/diagnóstico por imagem , Hipófise/cirurgia , Seio Esfenoidal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/cirurgia , Feminino , Humanos , Hipofisectomia/métodos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Septo Nasal/diagnóstico por imagem , Septo Nasal/cirurgia , Seio Esfenoidal/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Conchas Nasais/diagnóstico por imagem , Conchas Nasais/cirurgia , Adulto Jovem
18.
Cochlear Implants Int ; 17(6): 276-282, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27808008

RESUMO

OBJECTIVES: The diagnosis of non-organic hearing loss (NOHL) is a difficult but important issue during the assessment process for cochlear implantation (CI). We aim to identify the key factors in identifying patients with NOHL during CI assessment and present our local screening protocol for NOHL. METHODS: A retrospective review of patients referred to the Yorkshire Auditory Implant Service (YAIS) between 2003 and 2015 who were subsequently diagnosed with NOHL during the assessment. Patient demographic data, audiological and functional assessments were assessed. RESULTS: Thirty-two patients were included in the study. Mean age was 43 years (range 14-82 years). Male to female ratio was 1:1.7. Indicators of possible NOHL included a sudden deterioration in hearing (n = 21; 66%), mismatches in observed behaviour and either pure-tone audiogram (PTA) (n = 27; 84%) or functional testing (n = 20; 80%) and stapedial reflexes below reported audiological thresholds (n = 12; 46%). A mismatch in functional hearing and PTA was seen in 72% of patients. Patients with suspected NOHL were referred for further objective testing. All 23 patients who underwent objective testing had better hearing levels compared to reported hearing thresholds thus placing them outside of implant criteria. Five candidates were found to have normal hearing thresholds. DISCUSSION: NOHL can present a significant challenge to the implant team, particularly in the subgroup with a pre-existing organic hearing loss with non-organic overlay. We discuss the common features in this cohort of patients. CONCLUSIONS: To facilitate the identification of patients with NOHL, the YAIS has developed a screening protocol.


Assuntos
Audiometria de Tons Puros/estatística & dados numéricos , Implante Coclear , Perda Auditiva Funcional/diagnóstico , Seleção de Pacientes , Avaliação de Sintomas/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Limiar Auditivo , Feminino , Perda Auditiva Funcional/fisiopatologia , Perda Auditiva Funcional/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Valores de Referência , Estudos Retrospectivos , Estribo/fisiopatologia , Avaliação de Sintomas/estatística & dados numéricos , Adulto Jovem
19.
Nat Commun ; 7: 10723, 2016 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-26898399

RESUMO

Ice streams drain large portions of ice sheets and play a fundamental role in governing their response to atmospheric and oceanic forcing, with implications for sea-level change. The mechanisms that generate ice stream flow remain elusive. Basal sliding and/or bed deformation have been hypothesized, but ice stream beds are largely inaccessible. Here we present a comprehensive, multi-scale study of the internal structure of mega-scale glacial lineations (MSGLs) formed at the bed of a palaeo ice stream. Analyses were undertaken at macro- and microscales, using multiple techniques including X-ray tomography, thin sections and ground penetrating radar (GPR) acquisitions. Results reveal homogeneity in stratigraphy, kinematics, granulometry and petrography. The consistency of the physical and geological properties demonstrates a continuously accreting, shallow-deforming, bed and invariant basal conditions. This implies that ice stream basal motion on soft sediment beds during MSGL formation is accommodated by plastic deformation, facilitated by continuous sediment supply and an inefficient drainage system.

20.
Eur Arch Otorhinolaryngol ; 273(3): 567-71, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25736468

RESUMO

To determine whether an elderly population with hearing impairment can be adequately rehabilitated with a bone-conduction hearing aid and whether the putative relationship between the elderly and an increased complication rate is justified. The study design was a retrospective case note review with a postal and telephone questionnaire, which was carried out in a tertiary centre. All patients aged 60 or over underwent implantation with a bone-conduction aid between 2009 and 2013 for conductive, SSD or mixed hearing loss. Outcome measures were complication rates and quality of life assessment using the Glasgow Benefit Inventory. The influence of patient and surgical factors on the complication rate was assessed. Fifty-one patients were implanted. Mean age was 67 years (range 60-89 years). The mean benefit, satisfaction and global GBI scores were 70 % (range 0-100 %), 70 % (0-100 %) and 82 % (83-100 %), respectively. The residual disability was 18 % (0-25 %). The adverse skin reaction rate was 16 % and the fixture loss rate was 2 %. There was a demonstrable increase in the complication rate with the dermatome (45 %; 5 patients) compared to the Sheffield 'S' (13 %; 2 patients) or linear incision techniques (29 %; 7 patients). The bone-conduction hearing aids are ideal method of hearing rehabilitation in the elderly for all forms of hearing loss. It provides significant benefit with no increased complication rate, which is imperative if social isolation is to be avoided and cognition preserved in this growing elderly population.


Assuntos
Condução Óssea , Auxiliares de Audição , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Complicações Pós-Operatórias , Estudos Retrospectivos , Inquéritos e Questionários
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