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1.
Nature ; 627(8005): 759-762, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38538936

RESUMO

The early evolution of a supernova (SN) can reveal information about the environment and the progenitor star. When a star explodes in vacuum, the first photons to escape from its surface appear as a brief, hours-long shock-breakout flare1,2, followed by a cooling phase of emission. However, for stars exploding within a distribution of dense, optically thick circumstellar material (CSM), the first photons escape from the material beyond the stellar edge and the duration of the initial flare can extend to several days, during which the escaping emission indicates photospheric heating3. Early serendipitous observations2,4 that lacked ultraviolet (UV) data were unable to determine whether the early emission is heating or cooling and hence the nature of the early explosion event. Here we report UV spectra of the nearby SN 2023ixf in the galaxy Messier 101 (M101). Using the UV data as well as a comprehensive set of further multiwavelength observations, we temporally resolve the emergence of the explosion shock from a thick medium heated by the SN emission. We derive a reliable bolometric light curve that indicates that the shock breaks out from a dense layer with a radius substantially larger than typical supergiants.

2.
Clin Radiol ; 75(11): 878.e21-878.e28, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32709393

RESUMO

AIM: To compare the interobserver reliability and diagnostic accuracy of the British Thoracic Society (BTS) scale and other visual assessment criteria in the context of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)-computed tomography (CT) evaluation of solid pulmonary nodules (SPNs). MATERIALS AND METHODS: Fifty patients who underwent FDG PET-CT for assessment of a SPN were identified. Seven reporters with varied experience at four centres graded FDG uptake visually using the British Thoracic Society (BTS) four-point scale. Five reporters also scored SPNs according to three- and five-point visual assessment scales and using semi-quantitative assessment (maximum standardised uptake value [SUVmax]). Interobserver reliability was assessed with the intra-class correlation coefficient (ICC) and weighted Cohen's kappa (κ). Diagnostic performance was evaluated by receiver operator characteristic (ROC) analysis. RESULTS: Good interobserver reliability was demonstrated with the BTS scale (ICC=0.78, 95% confidence interval [CI]: 0.69-0.85) and five-point scale (ICC=0.78, 95 CI 0.68-0.86), whilst the three-point scale demonstrated moderate reliability (ICC=0.70, 95% CI: 0.59-0.80). Almost perfect agreement was achieved between two consultants (κ=0.85), and substantial agreement between two other consultants (κ=0.78) using the BTS scale. ROC curves for the BTS and five-point scales demonstrated equivalent accuracy (BTS area under the ROC curve [AUC]=0.768; five-point AUC=0.768). SUVmax was no more accurate compared to the BTS scale (SUVmax AUC=0.794; BTS AUC=0.768, p=0.43). CONCLUSIONS: The BTS scale can be applied reliably by reporters with varied levels of PET-CT reporting experience, across different centres and has a diagnostic performance that is not surpassed by alternative scales.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Nódulo Pulmonar Solitário/diagnóstico por imagem , Idoso , Feminino , Fluordesoxiglucose F18 , Humanos , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/normas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/estatística & dados numéricos , Reprodutibilidade dos Testes , Nódulo Pulmonar Solitário/diagnóstico
3.
Eur J Nucl Med Mol Imaging ; 46(13): 2790-2799, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31482428

RESUMO

PURPOSE: Incidence of anal squamous cell carcinoma (ASCC) is increasing, with curative chemoradiotherapy (CRT) as the primary treatment of non-metastatic disease. A significant proportion of patients have locoregional treatment failure (LRF), but distant relapse is uncommon. Accurate prognostication of progression-free survival (PFS) would help personalisation of CRT regimens. The study aim was to evaluate novel imaging pre-treatment features, to prognosticate for PFS in ASCC. METHODS: Consecutive patients with ASCC treated with curative intent at a large tertiary referral centre who underwent pre-treatment FDG-PET/CT were included. Radiomic feature extraction was performed using LIFEx software on baseline FDG-PET/CT. Outcome data (PFS) was collated from electronic patient records. Elastic net regularisation and feature selection were used for logistic regression model generation on a randomly selected training cohort and applied to a validation cohort using TRIPOD guidelines. ROC-AUC analysis was used to compare performance of a regression model encompassing standard clinical prognostic factors (age, sex, tumour and nodal stage-model A), a radiomic feature model (model B) and a combined radiomic/clinical model (model C). RESULTS: A total of 189 patients were included in the study, with 145 in the training cohort and 44 in the validation cohort. Median follow-up was 35.1 and 37. 9 months, respectively for each cohort, with 70.3% and 68.2% reaching this time-point with PFS. GLCM entropy (a measure of randomness of distribution of co-occurring pixel grey-levels), NGLDM busyness (a measure of spatial frequency of changes in intensity between nearby voxels of different grey-level), minimum CT value (lowest HU within the lesion) and SMTV (a standardized version of MTV) were selected for inclusion in the prognostic model, alongside tumour and nodal stage. AUCs for performance of model A (clinical), B (radiomic) and C (radiomic/clinical) were 0.6355, 0.7403, 0.7412 in the training cohort and 0.6024, 0.6595, 0.7381 in the validation cohort. CONCLUSION: Radiomic features extracted from pre-treatment FDG-PET/CT in patients with ASCC may provide better PFS prognosis than conventional staging parameters. With external validation, this might be useful to help personalise CRT regimens in the future.


Assuntos
Neoplasias do Ânus/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Fluordesoxiglucose F18 , Processamento de Imagem Assistida por Computador , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
Clin Radiol ; 74(8): 623-636, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31036310

RESUMO

Imaging of rectal cancer has an increasingly pivotal role in the diagnosis, staging, and treatment stratification of patients with the disease. This is particularly true for advanced rectal cancers where magnetic resonance imaging (MRI) findings provide essential information that can change treatment. In this review we describe the rationale for the current imaging standards in advanced rectal cancer for both morphological and functional imaging on the baseline staging and reassessment studies. In addition the clinical implications and future methods by which radiologists may improve these are outlined relative to TNM8.


Assuntos
Imageamento por Ressonância Magnética/métodos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Tomografia Computadorizada por Raios X/métodos , Humanos , Estadiamento de Neoplasias , Reto/diagnóstico por imagem , Reto/patologia
5.
Clin Radiol ; 74(8): 637-642, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31084973

RESUMO

AIM: To evaluate the current opinion of magnetic resonance imaging (MRI) reports amongst specialist clinicians involved in colorectal cancer multidisciplinary teams (CRC MDTs). MATERIALS AND METHODS: Active participants at 16 UK CRC MDTs across a population of 5.7 million were invited to complete a questionnaire, this included 22 closed and three open questions. Closed questions used ordinal (Likert) scales to judge the subjective inclusion of tumour descriptors and impressions on the clarity and consistency of the MRI report. Open (free-text) questions allowed overall feedback and suggestions. RESULTS: A total of 69 participants completed the survey (21 radiologists and 48 other CRC MDT clinicians). Both groups highlighted that reports commonly omit the status of the circumferential resection margin (CRM; 83% versus 81% inclusion, other clinicians and radiologists, respectively, p>0.05), presence or absence of extra-mural venous invasion (EMVI; 67% versus 57% inclusion, p>0.05), and lymph node status (90% inclusion in both groups). Intra-radiologist agreement across MRI examinations is reported as 75% by other clinicians. Free-text comments included suggestions for template-style reports. CONCLUSION: Both groups recognise a proportion of MRI reports are suboptimal with key tumour descriptors omitted. There are also concerns around the presentation style of MRI reports and inter- and intra-radiologist report variability. The widespread implementation of standardised report templates may improve completeness and clarity of MRI reports for rectal cancer and thus clinical management and outcomes in rectal cancer.


Assuntos
Atitude do Pessoal de Saúde , Imageamento por Ressonância Magnética/métodos , Equipe de Assistência ao Paciente , Radiologistas , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Humanos , Estadiamento de Neoplasias , Reto/diagnóstico por imagem , Reto/patologia , Reprodutibilidade dos Testes , Inquéritos e Questionários , Reino Unido
6.
Clin Exp Immunol ; 196(3): 287-304, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30985006

RESUMO

Plague caused by the Gram-negative bacterium, Yersinia pestis, is still endemic in parts of the world today. Protection against pneumonic plague is essential to prevent the development and spread of epidemics. Despite this, there are currently no licensed plague vaccines in the western world. Here we describe the means of delivering biologically active plague vaccine antigens directly to mucosal sites of plague infection using highly stable microvesicles (outer membrane vesicles; OMVs) that are naturally produced by the abundant and harmless human commensal gut bacterium Bacteroides thetaiotaomicron (Bt). Bt was engineered to express major plague protective antigens in its OMVs, specifically Fraction 1 (F1) in the outer membrane and LcrV (V antigen) in the lumen, for targeted delivery to the gastrointestinal (GI) and respiratory tracts in a non-human primate (NHP) host. Our key findings were that Bt OMVs stably expresses F1 and V plague antigens, particularly the V antigen, in the correct, immunogenic form. When delivered intranasally V-OMVs elicited substantive and specific immune and antibody responses, both in the serum [immunoglobulin (Ig)G] and in the upper and lower respiratory tract (IgA); this included the generation of serum antibodies able to kill plague bacteria. Our results also showed that Bt OMV-based vaccines had many desirable characteristics, including: biosafety and an absence of any adverse effects, pathology or gross alteration of resident microbial communities (microbiotas); high stability and thermo-tolerance; needle-free delivery; intrinsic adjuvanticity; the ability to stimulate both humoral and cell-mediated immune responses; and targeting of primary sites of plague infection.


Assuntos
Antígenos de Bactérias/metabolismo , Membrana Externa Bacteriana/metabolismo , Bacteroides thetaiotaomicron/metabolismo , Vacina contra a Peste/imunologia , Peste/imunologia , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Vesículas Transportadoras/imunologia , Yersinia pestis/fisiologia , Administração Intranasal , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/genética , Bacteroides thetaiotaomicron/genética , Bioengenharia , Morte Celular , Células Cultivadas , Microbioma Gastrointestinal/genética , Humanos , Imunidade Celular , Imunidade Humoral , Imunoglobulina A/metabolismo , Imunoglobulina G/sangue , Macaca , Peste/prevenção & controle , Vacina contra a Peste/metabolismo , Proteínas Citotóxicas Formadoras de Poros/genética , Vesículas Transportadoras/metabolismo
7.
Eur Radiol ; 29(9): 5121-5128, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30796574

RESUMO

PURPOSE: Rectal cancer staging with magnetic resonance imaging (MRI) allows accurate assessment and preoperative staging of rectal cancers. Therefore, complete MRI reports are vital to treatment planning. Significant variability may exist in their content and completeness. Template-style reporting can improve reporting standards, but its use is not widespread. Given the implications for treatment, we have evaluated current clinical practice amongst specialist gastrointestinal (GI) radiologists to measure the quality of rectal cancer staging MRI reports. MATERIALS AND METHODS: Sixteen United Kingdom (UK) colorectal cancer multi-disciplinary teams (CRC-MDTs) serving a population over 5 million were invited to submit up to 10 consecutive rectal cancer primary staging MRI reports from January 2016 for each radiologist participating in the CRC-MDT. Reports were compared to a reference standard based on recognised staging and prognostic factors influencing case management RESULTS: Four hundred ten primary staging reports were submitted from 41 of 42 (97.6%) eligible radiologists. Three hundred sixty reports met the inclusion criteria, of these, 81 (22.5%) used a template. Template report usage significantly increased recording of key data points versus non-template reports for extra-mural venous invasion (EMVI) status (98.8% v 51.6%, p < 0.01) and circumferential resection margin (CRM) status (96.3% v 65.9%, p < 0.01). Local tumour stage (97.5% v 93.5%, NS) and nodal status (98.8% v 96.1%, NS) were reported and with similar frequency. CONCLUSION: Rectal cancer primary staging reports do not meet published standards. Template-style reports have significant increases in the inclusion of key tumour descriptors. This study provides further support for their use to improve reporting standards and outcomes in rectal cancer. KEY POINTS: • MRI primary staging of rectal cancer requires detailed tumour descriptions as these alter the neoadjuvant and surgical treatments. • Currently, rectal cancer MRI reports in clinical practice do not provide sufficient detail on these tumour descriptors. • The use of template-style reports for primary staging of rectal cancer significantly improves report quality compared to free-text reports.


Assuntos
Controle de Formulários e Registros/normas , Imageamento por Ressonância Magnética/métodos , Estadiamento de Neoplasias/métodos , Melhoria de Qualidade , Neoplasias Retais/diagnóstico , Humanos , Padrões de Referência , Reino Unido
8.
J Phys Condens Matter ; 29(38): 385802, 2017 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-28677596

RESUMO

Polarised neutron diffraction measurements have been made on HoFeO3 single crystals magnetised in both the [0 0 1] and [1 0 0] directions (Pbnm setting). The polarisation dependencies of Bragg reflection intensities were measured both with a high field of [Formula: see text] T parallel to [0 0 1] at [Formula: see text] K and with the lower field [Formula: see text] T parallel to [1 0 0] at [Formula: see text] K. A Fourier projection of magnetization induced parallel to [0 0 1], made using the hk0 reflections measured in 9 T, indicates that almost all of it is due to alignment of Ho moments. Further analysis of the asymmetries of general reflections in these data showed that although, at 70 K, 9 T applied parallel to [0 0 1] hardly perturbs the antiferromagnetic order of the Fe sublattices, it induces significant antiferromagnetic order of the Ho sublattices in the [Formula: see text] plane, with the antiferromagnetic components of moment having the same order of magnitude as the induced ferromagnetic ones. Strong intensity asymmetries measured in the low temperature [Formula: see text] structure with a lower field, 0.5 T [Formula: see text] [1 0 0] allowed the variation of the ordered components of the Ho and Fe moments to be followed. Their absolute orientations, in the [Formula: see text] domain stabilised by the field were determined relative to the distorted perovskite structure. This relationship fixes the sign of the Dzyalshinski-Moriya (D-M) interaction which leads to the weak ferromagnetism. Our results indicate that the combination of strong y-axis anisotropy of the Ho moments and Ho-Fe exchange interactions breaks the centrosymmetry of the structure and could lead to ferroelectric polarization.

9.
Medchemcomm ; 7(9): 1793-1796, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28042453

RESUMO

Coactivator-associated arginine methyltransferase 1 (CARM1) is a type I protein arginine methyltransferase (PRMT) that catalyzes the conversion of arginine into monomethylarginine (MMA) and further into asymmetric dimethylarginine (ADMA). CARM1 methylates histone 3 arginines 17 and 26, as well as numerous non-histone proteins including CBP/p300, SRC-3, NCOA2, PABP1, and SAP49, while also functioning as a coactivator for various proteins that have been linked to cancer such as p53, NF-κß, ß-catenin, E2F1 and steroid hormone receptor ERα. As a result, CARM1 is involved in transcriptional activation, cellular differentiation, cell cycle progression, RNA splicing and DNA damage response. It has been associated with several human cancers including breast, colon, prostate and lung cancers and thus, is a potential oncological target. Herein, we present the design and synthesis of a series of CARM1 inhibitors. Based on a fragment hit, we discovered compound 9 as a potent inhibitor that displayed selectivity for CARM1 over other PRMTs.

10.
Leukemia ; 30(3): 605-16, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26500140

RESUMO

The FOXP1 (forkhead box P1) transcription factor is a marker of poor prognosis in diffuse large B-cell lymphoma (DLBCL). Here microarray analysis of FOXP1-silenced DLBCL cell lines identified differential regulation of immune response signatures and major histocompatibility complex class II (MHC II) genes as some of the most significant differences between germinal center B-cell (GCB)-like DLBCL with full-length FOXP1 protein expression versus activated B-cell (ABC)-like DLBCL expressing predominantly short FOXP1 isoforms. In an independent primary DLBCL microarray data set, multiple MHC II genes, including human leukocyte antigen DR alpha chain (HLA-DRA), were inversely correlated with FOXP1 transcript expression (P<0.05). FOXP1 knockdown in ABC-DLBCL cells led to increased cell-surface expression of HLA-DRA and CD74. In R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-treated DLBCL patients (n=150), reduced HLA-DRA (<90% frequency) expression correlated with inferior overall survival (P=0.0003) and progression-free survival (P=0.0012) and with non-GCB subtype stratified by the Hans, Choi or Visco-Young algorithms (all P<0.01). In non-GCB DLBCL cases with <90% HLA-DRA, there was an inverse correlation with the frequency (P=0.0456) and intensity (P=0.0349) of FOXP1 expression. We propose that FOXP1 represents a novel regulator of genes targeted by the class II MHC transactivator CIITA (MHC II and CD74) and therapeutically targeting the FOXP1 pathway may improve antigen presentation and immune surveillance in high-risk DLBCL patients.


Assuntos
Antígenos de Diferenciação de Linfócitos B/imunologia , Linfócitos B/imunologia , Fatores de Transcrição Forkhead/imunologia , Regulação Neoplásica da Expressão Gênica , Antígenos de Histocompatibilidade Classe II/imunologia , Linfoma Difuso de Grandes Células B/genética , Proteínas Nucleares/imunologia , Proteínas Repressoras/imunologia , Transativadores/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/uso terapêutico , Antígenos de Diferenciação de Linfócitos B/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos B/efeitos dos fármacos , Linfócitos B/patologia , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Fatores de Transcrição Forkhead/antagonistas & inibidores , Fatores de Transcrição Forkhead/genética , Centro Germinativo/efeitos dos fármacos , Centro Germinativo/imunologia , Centro Germinativo/patologia , Cadeias alfa de HLA-DR/genética , Cadeias alfa de HLA-DR/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Ativação Linfocitária , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas Nucleares/genética , Prednisona/uso terapêutico , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/imunologia , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/genética , Rituximab , Transdução de Sinais , Análise de Sobrevida , Transativadores/genética , Vincristina/uso terapêutico
11.
Aliment Pharmacol Ther ; 41(3): 293-300, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25521607

RESUMO

BACKGROUND: Psoriasis has been linked to metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Data suggest that the prevalence of NAFLD is increased in patients with psoriasis. The aim of this study was to determine the prevalence and severity of NAFLD in this patient population. AIM: To determine the prevalence of both NAFLD and non-alcoholic steatohepatitis (NASH) in patients with psoriasis. METHODS: Patients between the ages of 18 and 70 years with a diagnosis of psoriasis or psoriatic arthritis and followed by either the Dermatology or Rheumatology Division within the Department of Medicine at San Antonio Military Medical Center were considered for enrollment. Each patient completed a questionnaire, underwent a thorough skin evaluation, and had a right upper quadrant ultrasound and fasting blood work. If the liver enzymes were elevated or fatty liver detected on imaging, percutaneous liver biopsy was recommended. RESULTS: One hundred and twenty-nine patients were enrolled and 103 completed all necessary studies. The participants were predominantly middle aged (52.7 ± 12) and overweight or obese (average BMI 30.1 ± 5.9, range: 19.8-52.5 kg/m(2)). 53% (n = 54) were male while 15% (n = 15) of participants identified themselves as being a diabetic. The overall prevalence of NAFLD was 47%. The overall prevalence of NASH was 22% in those who underwent biopsy. CONCLUSIONS: Non-alcoholic fatty liver disease is very common among our cohort of patients with psoriasis, occurring in roughly 47% of patients. The more progressive form of the disease, NASH, is found in approximately one in five patients. Health care providers should be mindful of this association given the high prevalence of both NAFLD and NASH in this cohort of patients.


Assuntos
Fígado Gorduroso/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Psoríase/complicações , Adulto , Idoso , Biópsia , Diabetes Mellitus/epidemiologia , Fígado Gorduroso/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Prevalência , Inquéritos e Questionários
12.
G3 (Bethesda) ; 4(9): 1593-602, 2014 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-25237111

RESUMO

Sorghum varieties suitable for grain production at temperate latitudes show dwarfism and photoperiod insensitivity, both of which are controlled by a small number of loci with large effects. We studied the genetic control of plant height and flowering time in five sorghum families (A-E), each derived from a cross between a tropical line and a partially isogenic line carrying introgressions derived from a common, temperate-adapted donor. A total of 724 F2:3 lines were phenotyped in temperate and tropical environments for plant height and flowering time and scored at 9139 SNPs using genotyping-by-sequencing. Biparental mapping was compared with multiparental mapping in different subsets of families (AB, ABC, ABCD, and ABCDE) using both a GWAS approach, which fit each QTL as a single effect across all families, and using a joint linkage approach, which fit QTL effects as nested within families. GWAS using all families (ABCDE) performed best at the cloned Dw3 locus, whereas joint linkage using all families performed best at the cloned Ma1 locus. Both multiparental approaches yielded apparently synthetic associations due to genetic heterogeneity and were highly dependent on the subset of families used. Comparison of all mapping approaches suggests that a GA2-oxidase underlies Dw1, and that a mir172a gene underlies a Dw1-linked flowering time QTL.


Assuntos
Locos de Características Quantitativas , Sorghum/genética , Mapeamento Cromossômico , Cromossomos de Plantas , Flores/fisiologia , Ligação Genética , Genoma de Planta , Estudo de Associação Genômica Ampla , Genótipo , Fenótipo , Polimorfismo de Nucleotídeo Único , Sorghum/crescimento & desenvolvimento , Sorghum/fisiologia
13.
Appl Clin Inform ; 5(2): 430-44, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25024759

RESUMO

OBJECTIVE: Several studies have documented the preference for physicians to attend to the impression and plan section of a clinical document. However, it is not clear how much attention other sections of a document receive. The goal of this study was to identify how physicians distribute their visual attention while reading electronic notes. METHODS: We used an eye-tracking device to assess the visual attention patterns of ten hospitalists as they read three electronic notes. The assessment included time spent reading specific sections of a note as well as rates of reading. This visual analysis was compared with the content of simulated verbal handoffs for each note and debriefing interviews. RESULTS: Study participants spent the most time in the "Impression and Plan" section of electronic notes and read this section very slowly. Sections such as the "Medication Profile", "Vital Signs" and "Laboratory Results" received less attention and were read very quickly even if they contained more content than the impression and plan. Only 9% of the content of physicians' verbal handoff was found outside of the "Impression and Plan." CONCLUSION: Physicians in this study directed very little attention to medication lists, vital signs or laboratory results compared with the impression and plan section of electronic notes. Optimizing the design of electronic notes may include rethinking the amount and format of imported patient data as this data appears to largely be ignored.


Assuntos
Atenção , Registros Eletrônicos de Saúde/estatística & dados numéricos , Médicos/psicologia , Leitura , Adulto , Movimentos Oculares , Feminino , Humanos , Masculino , Planejamento de Assistência ao Paciente
14.
Leukemia ; 28(2): 362-72, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23884370

RESUMO

We previously identified autoantibodies to the endocytic-associated protein Huntingtin-interacting protein 1-related (HIP1R) in diffuse large B-cell lymphoma (DLBCL) patients. HIP1R regulates internalization of cell surface receptors via endocytosis, a process relevant to many therapeutic strategies including CD20 targeting with rituximab. In this study, we characterized HIP1R expression patterns, investigated a mechanism of transcriptional regulation and its clinical relevance in DLBCL patients treated with immunochemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone, R-CHOP). HIP1R was preferentially expressed in germinal center B-cell-like DLBCL (P<0.0001) and inversely correlated with the activated B-cell-like DLBCL (ABC-DLBCL) associated transcription factor, Forkhead box P1 (FOXP1). HIP1R was confirmed as a direct FOXP1 target gene in ABC-DLBCL by FOXP1-targeted silencing and chromatin immunoprecipitation. Lower HIP1R protein expression (≤ 10% tumoral positivity) significantly correlated with inferior overall survival (OS, P=0.0003) and progression-free survival (PFS, P=0.0148) in R-CHOP-treated DLBCL patients (n=157). Reciprocal expression with ≥ 70% FOXP1 positivity defined FOXP1(hi)/HIP1R(lo) patients with particularly poor outcome (OS, P=0.0001; PFS, P=0.0016). In an independent R-CHOP-treated DLBCL (n=233) microarray data set, patients with transcript expression in lower quartile HIP1R and FOXP1(hi)/HIP1R(lo) subgroups exhibited worse OS, P=0.0044 and P=0.0004, respectively. HIP1R repression by FOXP1 is strongly associated with poor outcome, thus further understanding of FOXP1-HIP1R and/or endocytic signaling pathways might give rise to novel therapeutic options for DLBCL.


Assuntos
Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Proteínas Repressoras/genética , Proteínas de Transporte Vesicular/genética , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos B/metabolismo , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Proteínas dos Microfilamentos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/uso terapêutico , Prognóstico , Ligação Proteica , Proteínas Repressoras/metabolismo , Rituximab , Resultado do Tratamento , Proteínas de Transporte Vesicular/metabolismo , Vincristina/uso terapêutico , Adulto Jovem
15.
J Phys Condens Matter ; 25(23): 236004, 2013 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-23685626

RESUMO

The polarization dependence of the intensity of elastic magnetic scattering from YMn2O5 single crystals has been measured at 25 K in magnetic fields between 1 and 9 T. A significant polarization dependence was observed in the intensities of magnetic satellite reflections, propagation vector τ = ½, 0, », measured with both the [100] and [010] axes parallel to the common polarization and applied field direction. The intensity asymmetries A observed in sets of orthorhombic equivalent reflections show systematic relationships which allow the phase relationship between different components of their magnetic interaction vectors to be determined. They fix the orientation relationships between the small y and z moments on the Mn(4+) and Mn(3+) sub-lattices and have allowed a further refinement of the magnetic structure, which determines the phases of the vector Fourier components with much higher precision. Systematic differences found between values of A(hkl) and A(h¯k¯l¯) suggest that there is a small modulation of the nuclear structure which has the same wavevector as the magnetic modulation and gives rise to a small nuclear structure factor for the satellite reflections. The magnitudes of the differences suggest shifts in the atomic positions of the order of 0.05 Å.

16.
J Phys Condens Matter ; 25(20): 206002, 2013 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-23612471

RESUMO

The magnetization distribution in Co2FeSi which has the largest moment per formula unit ∼6 µB of all Heusler alloys, has been determined using polarized neutron diffraction. The experimentally determined magnetization has been integrated over spheres centred on the three sites of the L12 structure giving µ Fe = 3.10(3) µB and µ Co = 1.43(2) µB, results which are slightly lower than the moments in atomic spheres of similar radii obtained in recent LDA + U band structure calculations (Li et al 2010 Chin. Phys. B 19 097102). Approximately 50% of the magnetic carriers at the Fe sites were found to be in orbitals with eg symmetry. This was higher, ≃65%, at the Co sites. Both Fe and Co were found to have orbital moments that are larger than those predicted. Comparison with similar results obtained for related alloys suggests that there must be a finite density of states in both spin bands at the Fermi energy indicating that Co2FeSi is not a perfect half-metallic ferromagnet.

17.
Clin Pharmacol Ther ; 92(6): 689-93, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23093316

RESUMO

Epigenetic control of gene expression occurs at two distinctlevels: DNA methylation and histone modification. Over thepast 10 years, the discovery of epigenetic targets has acceleratedto the point where more than 400 domains have beenidentified that are involved in either DNA methylation, themodification of histones (and some nonhistones), or translationof these modifications into changes in gene expression


Assuntos
Epigênese Genética/genética , Epigenômica/métodos , Animais , Metilação de DNA , Regulação da Expressão Gênica/fisiologia , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Humanos , Lisina/metabolismo
18.
Phys Rev Lett ; 108(23): 237201, 2012 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-23003983

RESUMO

The coupling of magnetic chiralities to the ferroelectric polarization in multiferroic RbFe(MoO4)2 is investigated by neutron spherical polarimetry. Because of the axiality of the crystal structure below T(c)=190 K, helicity and triangular chirality are symmetric-exchange coupled, explaining the onset of the ferroelectricity in this proper-screw magnetic structure--a mechanism that can be generalized to other systems with ferroaxial distortions in the crystal structure. With an applied electric field, we demonstrate control of the chiralities in both structural domains simultaneously.

19.
J Comp Pathol ; 147(2-3): 181-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22520810

RESUMO

The histological and immunohistochemical features of 13 cases of suspected vaginal fibroepithelial polyps are reported. The characteristic microscopical features of these lesions were an abundant oedematous or fibrous stroma containing spindle-shaped and stellate cells and the presence of variable inflammation and haemorrhage. There was often a superficial layer of compressed tissue, but the stroma in the peripheral areas of the masses was generally more loosely arranged than in central areas. The connective tissue cells expressed vimentin and desmin, but did not express smooth muscle actin or calponin. Individual cases had additional changes including granulomatous inflammation, epithelial dysplasia suggestive of papillomavirus infection and a lesion resembling phyllodes tumour in women.


Assuntos
Doenças do Cão/patologia , Neoplasias Fibroepiteliais/veterinária , Pólipos/veterinária , Neoplasias Vaginais/veterinária , Animais , Biomarcadores Tumorais/metabolismo , Desmina/metabolismo , Doenças do Cão/metabolismo , Cães , Feminino , Neoplasias Fibroepiteliais/metabolismo , Neoplasias Fibroepiteliais/patologia , Pólipos/metabolismo , Pólipos/patologia , Neoplasias Vaginais/metabolismo , Neoplasias Vaginais/patologia , Vimentina/metabolismo
20.
Reprod Domest Anim ; 47(5): 740-5, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22136299

RESUMO

Congenital abnormalities of the reproductive tract of male sheep were surveyed at three abattoirs in the south west of England during the period June 2000-January 2004. A total of 7307 rams were examined [6521 lambs (prepubescent) and hoggets (aged from their first autumn after birth until first shorn) and 786 adult rams mature rams that had been exposed to ewes]. A total of 156 congenital lesions were detected, 87 of which occurred in lambs. Testicular hypoplasia was the most common lesion occurring in 69 lambs as well as eight hoggets ('microtestes' were recognized in nine other animals in which the testis was disproportionately smaller than the epididymis). The second most common lesion found was notched scrotum occurring in 34 animals (27 young rams and seven adults). Some cases of notched scrotum were accompanied by hypospadias which was seen in a total of seven lambs and eight hoggets. Other lesions, detected in five or less animals (less than approximately 0.05% of the animals examined), included cryptorchidism and various abnormalities of the epididymis (segmental aplasia of the epididymis, blind efferent ducts and epididymal cyst) and congenital scrotal hernia. The overall prevalence of congenital lesions of 2.21% emphasizes the importance of undertaking breeding soundness examinations of young rams before they are put with the flock.


Assuntos
Genitália Masculina/anormalidades , Doenças dos Ovinos/epidemiologia , Ovinos/anormalidades , Matadouros , Animais , Criptorquidismo/epidemiologia , Criptorquidismo/veterinária , Inglaterra/epidemiologia , Epididimo/anormalidades , Hipospadia/epidemiologia , Hipospadia/veterinária , Masculino , Escroto/anormalidades , Maturidade Sexual , Doenças dos Ovinos/diagnóstico por imagem , Testículo/anormalidades , Ultrassonografia
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