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1.
Leukemia ; 38(4): 720-728, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38360863

RESUMEN

Current strategies to treat pediatric acute lymphoblastic leukemia rely on risk stratification algorithms using categorical data. We investigated whether using continuous variables assigned different weights would improve risk stratification. We developed and validated a multivariable Cox model for relapse-free survival (RFS) using information from 21199 patients. We constructed risk groups by identifying cutoffs of the COG Prognostic Index (PICOG) that maximized discrimination of the predictive model. Patients with higher PICOG have higher predicted relapse risk. The PICOG reliably discriminates patients with low vs. high relapse risk. For those with moderate relapse risk using current COG risk classification, the PICOG identifies subgroups with varying 5-year RFS. Among current COG standard-risk average patients, PICOG identifies low and intermediate risk groups with 96% and 90% RFS, respectively. Similarly, amongst current COG high-risk patients, PICOG identifies four groups ranging from 96% to 66% RFS, providing additional discrimination for future treatment stratification. When coupled with traditional algorithms, the novel PICOG can more accurately risk stratify patients, identifying groups with better outcomes who may benefit from less intensive therapy, and those who have high relapse risk needing innovative approaches for cure.


Asunto(s)
Linfoma de Burkitt , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Humanos , Adulto Joven , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Pronóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recurrencia , Medición de Riesgo , Supervivencia sin Enfermedad
2.
Nat Commun ; 12(1): 334, 2021 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-33436570

RESUMEN

Magnetized plasma interactions are ubiquitous in astrophysical and laboratory plasmas. Various physical effects have been shown to be important within colliding plasma flows influenced by opposing magnetic fields, however, experimental verification of the mechanisms within the interaction region has remained elusive. Here we discuss a laser-plasma experiment whereby experimental results verify that Biermann battery generated magnetic fields are advected by Nernst flows and anisotropic pressure effects dominate these flows in a reconnection region. These fields are mapped using time-resolved proton probing in multiple directions. Various experimental, modelling and analytical techniques demonstrate the importance of anisotropic pressure in semi-collisional, high-ß plasmas, causing a reduction in the magnitude of the reconnecting fields when compared to resistive processes. Anisotropic pressure dynamics are crucial in collisionless plasmas, but are often neglected in collisional plasmas. We show pressure anisotropy to be essential in maintaining the interaction layer, redistributing magnetic fields even for semi-collisional, high energy density physics (HEDP) regimes.

3.
Respir Med ; 175: 106154, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33190085

RESUMEN

BACKGROUND: Combination low-dose budesonide-formoterol, taken as-needed for symptom relief reduces exacerbation risk and is recommended for treatment of mild asthma. The NovelQ qualitative study explored patients' attitudes toward using this novel therapy. METHODS: Adults with mild asthma using reliever-only treatment were randomised to as-needed budesonide-formoterol Turbuhaler® in a multinational, 52-week open-label randomised controlled trial (NovelSTART-ACTRN12615000999538). A subgroup were interviewed to explore their attitudes to use of as-needed budesonide-formoterol after receiving it for ≥10 months. Semi-structured interviews were conducted until saturation, audio-recorded, and thematically analysed. RESULTS: Analysis of 35 participants (66% female; mean age 43.5 [range 18-74]; mean Asthma Control Questionnaire score 1.09 ± SD0.55) interviews identified 5 themes, each including both barriers and facilitators to therapy use. Themes were: 'Treatment effectiveness' i.e. how well symptoms were relieved and/or prevented; 'Lifestyle fit of the regimen' e.g. the extent to which the treatment regimen integrated into the patient's daily life; 'Attitudes toward medication use and safety' e.g. openness for new reliever treatments, beliefs about treatment necessity or side effects; 'Device attributes' e.g. perceived ease of use; and 'Doctor-patient relationship' e.g. impact of health professional support on new treatment acceptance. CONCLUSIONS: A wide range of factors seem to drive the opinions of mild asthma patients on as-needed budesonide-formoterol therapy. Many patients perceived both positive and negative treatment attributes, and their individual evaluation of these attributes determined their likelihood of using it after the study. Supportive patient-physician interactions appear key to addressing patient barriers. Recommendations for patient-centred discussions, developed from this research, are provided.


Asunto(s)
Asma/tratamiento farmacológico , Asma/psicología , Combinación Budesonida y Fumarato de Formoterol/administración & dosificación , Nebulizadores y Vaporizadores , Investigación Cualitativa , Administración por Inhalación , Adolescente , Adulto , Anciano , Actitud Frente a la Salud , Femenino , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Prioridad del Paciente , Relaciones Médico-Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad , Adulto Joven
4.
J Asthma ; 55(9): 1018-1027, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29064746

RESUMEN

Objective: Young people with asthma often lack engagement in self-management. Smartphone apps offer an attractive, immediate method for obtaining asthma information and self-management support. In this research we developed an evidence-based asthma app tailored to young peoples needs, created using a participatory design approach to optimize user engagement. This paper describes the participatory design process. Methods: This multi-phased research included concept generation and ideation of app design by young people with asthma, and development of asthma information by the research team. Clinical review was sought regarding safety and accuracy of app content. Participants suggestions for improvement and any problems with the app were logged throughout. Our young co-designers were invited back to test a high fidelity prototype app using a "think aloud" process and completed a usability questionnaire. Results: Twenty asthma patients aged 15-24 years contributed to the initial app design. Three respiratory specialists and two pharmacists suggested minor corrections to clinical terminology in the app which were all incorporated. Nine co-designers acted as expert reviewers of the prototype app, of whom eight completed a usability questionnaire. Median usability scores (maximum score 6) indicated high satisfaction with app content, usefulness and ease of use [median item score 5.3 (range 4.7-6.0)]. All feedback was incorporated to create an updated prototype app. Conclusions: A clinically sound asthma app has been developed which is considered highly acceptable to the young co-designers. A six-week test of the engagement, acceptability, and usefulness of the app in young people not involved in the participatory design will follow.


Asunto(s)
Asma/terapia , Aplicaciones Móviles , Automanejo/métodos , Diseño de Software , Adolescente , Femenino , Humanos , Masculino , Satisfacción del Paciente , Pacientes/psicología , Farmacéuticos/psicología , Proyectos de Investigación , Terapia Respiratoria/métodos , Telemedicina , Adulto Joven
5.
Phys Rev Lett ; 119(5): 055001, 2017 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-28949745

RESUMEN

We present new experiments to study the formation of radiative shocks and the interaction between two counterpropagating radiative shocks. The experiments are performed at the Orion laser facility, which is used to drive shocks in xenon inside large aspect ratio gas cells. The collision between the two shocks and their respective radiative precursors, combined with the formation of inherently three-dimensional shocks, provides a novel platform particularly suited for the benchmarking of numerical codes. The dynamics of the shocks before and after the collision are investigated using point-projection x-ray backlighting while, simultaneously, the electron density in the radiative precursor was measured via optical laser interferometry. Modeling of the experiments using the 2D radiation hydrodynamic codes nym and petra shows very good agreement with the experimental results.

6.
Nat Commun ; 7: ncomms11899, 2016 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-27291065

RESUMEN

Astrophysical flows exhibit rich behaviour resulting from the interplay of different forms of energy-gravitational, thermal, magnetic and radiative. For magnetic cataclysmic variable stars, material from a late, main sequence star is pulled onto a highly magnetized (B>10 MG) white dwarf. The magnetic field is sufficiently large to direct the flow as an accretion column onto the poles of the white dwarf, a star subclass known as AM Herculis. A stationary radiative shock is expected to form 100-1,000 km above the surface of the white dwarf, far too small to be resolved with current telescopes. Here we report the results of a laboratory experiment showing the evolution of a reverse shock when both ionization and radiative losses are important. We find that the stand-off position of the shock agrees with radiation hydrodynamic simulations and is consistent, when scaled to AM Herculis star systems, with theoretical predictions.

7.
Sci Rep ; 6: 24211, 2016 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-27071341

RESUMEN

The elastic and inelastic response of [001] oriented silicon to laser compression has been a topic of considerable discussion for well over a decade, yet there has been little progress in understanding the basic behaviour of this apparently simple material. We present experimental x-ray diffraction data showing complex elastic strain profiles in laser compressed samples on nanosecond timescales. We also present molecular dynamics and elasticity code modelling which suggests that a pressure induced phase transition is the cause of the previously reported 'anomalous' elastic waves. Moreover, this interpretation allows for measurement of the kinetic timescales for transition. This model is also discussed in the wider context of reported deformation of silicon to rapid compression in the literature.

8.
Br J Cancer ; 113(1): 57-63, 2015 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-26035700

RESUMEN

BACKGROUND: MYCN amplification with subsequent MYCN protein overexpression is a powerful indicator of poor prognosis of neuroblastoma patients. Little is known regarding the prognostic significance of the homologous MYC protein expression in neuroblastoma. METHODS: Immunostaining for MYCN and MYC protein was performed on 357 undifferentiated/poorly differentiated neuroblastomas. Results were analysed with other prognostic markers. RESULTS: Sixty-seven (19%) tumours were MYCN(+), 38 (11%) were MYC(+), and one(0.3%) had both proteins(+). MYCN(+) tumours and MYC(+) tumours were more likely diagnosed in children>18months with stage4-disease. MYCN(+) tumours were associated with amplified MYCN, Unfavourable Histology (UH), and High-MKI (Mitosis-Karyorrhexis Index). MYC(+) tumours were also frequently UH but not associated with MYCN amplification, and more likely to have low-/intermediate-MKI. Favourable Histology patients without MYC/MYCN expressions exhibited the best survival (N=167, 89.7±5.5% 3-year EFS, 97.0±3.2% 3-year OS), followed by UH patients without MYC/MYCN expressions (N=84, 63.1±13.6% 3-year EFS, 83.5±9.4% 3-year OS). MYCN(+)patients and MYC(+)patients had similar and significantly low (P<0.0001) survivals (46.2±12.0% 3-year EFS, 63.2±12.1% 3-year OS and 43.4±23.1% 3-year EFS, 63.5±19.2% 3-year OS, respectively). Notably, the prognostic impact imparted by MYC expression was independent from other markers. CONCLUSIONS: In this series, ∼30% of neuroblastomas had augmented MYCN or MYC expression with dismal survivals. Prospective study of MYC/MYCN protein expression signature as a new biomarker for high-risk neuroblastomas should be conducted.


Asunto(s)
Genes myc , Neuroblastoma/patología , Proteínas Nucleares/fisiología , Proteínas Oncogénicas/fisiología , Diferenciación Celular , Niño , Estudios de Cohortes , Humanos , Proteína Proto-Oncogénica N-Myc , Neuroblastoma/genética , Proteínas Nucleares/genética , Proteínas Oncogénicas/genética , Pronóstico
10.
Mol Pharm ; 11(11): 3930-7, 2014 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-24992368

RESUMEN

Cholecystokinin-2 (CCK-2) receptors, overexpressed in cancer types such as small cell lung cancers (SCLC) and medullary thyroid carcinomas (MTC), may serve as targets for peptide receptor radionuclide imaging. A variety of CCK and gastrin analogues has been developed, but a major drawback is metabolic instability or high kidney uptake. The minigastrin analogue PP-F11 has previously been shown to be a promising peptide for imaging of CCK-2 receptor positive tumors and was therefore further evaluated. The peptide was conjugated with one of the macrocyclic chelators DOTA, NOTA, or NODAGA. The peptide conjugates were then radiolabeled with either (68)Ga, (64)Cu, or (111)In. All (radio)labeled compounds were evaluated in vitro (IC50) and in vivo (biodistribution and PET/CT and SPECT/CT imaging). IC50 values were in the low nanomolar range for all compounds (0.79-1.51 nM). In the biodistribution studies, (68)Ga- and (111)In-labeled peptides showed higher tumor-to-background ratios than the (64)Cu-labeled compounds. All tested radiolabeled compounds clearly visualized the CCK2 receptor positive tumor in PET or SPECT imaging. The chelator did not seem to affect in vivo behavior of the peptide for (111)In- and (68)Ga-labeled peptides. In contrast, the biodistribution of the (64)Cu-labeled peptides showed high uptake in the liver and in other organs, most likely caused by high blood levels, probably due to dissociation of (64)Cu from the chelator and subsequent transchelation to proteins. Based on the present study, (68)Ga-DOTA-PP-F11 might be a promising radiopharmaceutical for PET/CT imaging of CCK2 receptor expressing tumors such as MTC and SCLC. Clinical studies are warranted to investigate the potential of this tracer.


Asunto(s)
Acetatos/farmacología , Radioisótopos de Cobre/química , Radioisótopos de Galio/química , Gastrinas/química , Compuestos Heterocíclicos con 1 Anillo/farmacología , Compuestos Heterocíclicos/farmacología , Radioisótopos de Indio/química , Animales , Línea Celular Tumoral , Quelantes/química , Femenino , Humanos , Concentración 50 Inhibidora , Ratones , Ratones SCID , Imagen Multimodal , Trasplante de Neoplasias , Péptidos/química , Tomografía de Emisión de Positrones , Radiofármacos/química , Receptor de Colecistoquinina B/metabolismo , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos X
11.
Acta Paediatr ; 103(10): e439-43, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24919409

RESUMEN

AIM: To test the hypothesis that there are single-nucleotide polymorphisms (SNPs) in genes of the l-arginine/nitric oxide pathway associated with pulmonary hypertension (PH) in neonates with bronchopulmonary dysplasia (BPD). METHODS: Neonates with BPD were enrolled (n = 140) and clinical characteristics compared between case (BPD + PH) and control (BPD) groups. DNA was isolated from blood leucocytes and assayed for 17 SNPs in l-arginine/nitric oxide pathway genes by Sequenom massarray. Genes included carbamoyl-phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthase, nitric oxide synthase and arginase. SNPs were selected from the National Center for Biotechnology Information database for their putative functionality. Calculated minor allele frequencies (MAF) of cases and controls were compared using χ2 and logistic regression. RESULTS: Of the 140 patients with BPD, 26% had echocardiographic evidence of PH. Ventilation days were longer for cases than controls (mean 31 vs. 15 days, p < 0.05). Of the 17 SNPs, rs2781666 in arginase I gene was less common in cases (MAF = 0.23) than controls (MAF = 0.37, p = 0.04). The odds of PH decreased by 43% (p = 0.047) for each copy of the SNP minor allele in arginase I gene in patients with BPD. CONCLUSION: Arginase I SNP (rs2781666) may be associated with protection against pulmonary hypertension in preterm neonates with BPD.


Asunto(s)
Arginasa/genética , Displasia Broncopulmonar/complicaciones , Hipertensión Pulmonar/genética , Estudios de Casos y Controles , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Polimorfismo de Nucleótido Simple
12.
Allergy ; 69(3): 372-9, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24444382

RESUMEN

BACKGROUND: Side-effect concerns impede adherence with inhaled corticosteroids (ICS) and often underlie poor asthma control. We developed a brief version (ICQ-S) of the 57-item Inhaled Corticosteroids side-effect Questionnaire (ICQ) to facilitate side-effect monitoring in busy clinics. METHODS: Part 1: After completion by 482 patients with doctor-diagnosed asthma, each ICQ item underwent item reduction analysis. Part 2: Patients prescribed ICS for asthma completed the ICQ at baseline (BL), ICQ-S at day 14 (D14) and day 28 (D28), and 6-item Asthma Control Questionnaire (ACQ) and Mini Asthma Quality of Life Questionnaire (MiniAQLQ) at BL, D14 and D28. 14-day test-retest reliability was assessed by intraclass correlation coefficient (ICC) between ICQ-S scores and internal consistency by Cronbach's alpha (α) coefficient and item-total correlations of ICQ-S. Criterion validity was assessed by correlations (Spearman's rho) between ICQ and ICQ-S total score. Patients reported duration and difficulty of ICQ-S completion at D28. RESULTS: Part 1: The ICQ-S consists of fifteen local/systemic ICS side-effects of similar range to the full ICQ. Part 2: 62 asthma patients (mean ACQ score 0.79 ± SD 0.83) prescribed daily ICS [BDP-equivalent median dose 1000 µg (IQR: 500, 1000)] participated. ICC between ICQ-S scores was 0.90. All item-total correlations were rho ≥ 0.20. The ICQ-S demonstrated criterion validity, for example, ICQ and ICQ-S were strongly associated (rho = 0.86). 81% of patients completed the ICQ-S within 5 minutes and 97% found completion 'not difficult'. CONCLUSION: The ICQ-S is a brief, patient-friendly tool with good reliability and validity, which may be useful for monitoring ICS side-effects in clinical practice.


Asunto(s)
Corticoesteroides/efectos adversos , Antiasmáticos/efectos adversos , Asma/epidemiología , Administración por Inhalación , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Adulto , Anciano , Antiasmáticos/administración & dosificación , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Reproducibilidad de los Resultados , Factores de Riesgo , Encuestas y Cuestionarios
13.
Acta Physiol (Oxf) ; 209(2): 148-55, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23841645

RESUMEN

AIM: During type 1 diabetes (T1D), the medullary thick ascending limb (mTAL) displays an NADPH oxidase-dependent increase in sodium transport, in concert with increased NO production by NO synthase 1 (NOS1) and NOS2. We hypothesized that NOS1- and/or NOS2-derived NO blunts T1D-induced activation of sodium transport in the mTAL. METHODS: T1D was induced by streptozotocin injection (STZ rats); sham rats received vehicle. Three-to-four weeks later, mTAL were isolated from both groups for assay of nitrite and superoxide production, and O2 consumption in the absence or presence of various inhibitors. RESULTS: Apocynin (NADPH oxidase inhibitor) normalized superoxide production and ouabain-sensitive O2 consumption and furosemide-sensitive O2 consumption by mTALs from STZ rats, without altering O2 consumption by mTALs from sham rats. Apocynin also unmasked a T1D-induced increase in nitrite production. NOS inhibition did not alter superoxide production in either group. In sham mTAL, total NOS inhibition, but not isoform-specific inhibition of NOS1 or NOS2, increased ouabain- and furosemide-sensitive O2 consumption, confirming a tonic inhibitory impact of NOS3 on sodium transport. In contrast, neither total nor isoform-specific NOS inhibition altered O2 consumption by STZ mTAL. Apocynin treatment of STZ mTAL unveiled the ability of isoform-specific NOS inhibition to significantly increase O2 consumption, without further increase in O2 consumption with total NOS inhibition. CONCLUSION: Under normal conditions, NOS3-derived NO inhibits sodium transport in the mTAL. T1D dismantles the impact of NOS-mediated inhibition of sodium transport as a result of NADPH oxidase-dependent NO scavenging. Inhibition of NADPH oxidase to preserve NO bioavailability reveals an inhibitory impact of NOS1- and NOS2-derived NO on sodium transport in the mTAL.


Asunto(s)
Diabetes Mellitus Experimental/metabolismo , NADPH Oxidasas/metabolismo , Nefronas/metabolismo , Óxido Nítrico Sintasa/metabolismo , Sodio/metabolismo , Animales , Diabetes Mellitus Tipo 1/metabolismo , Transporte Iónico/fisiología , Masculino , Nefronas/fisiopatología , Ratas , Ratas Sprague-Dawley
14.
Plant Dis ; 97(8): 1037-1041, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30722468

RESUMEN

Phytophthora capsici is a soilborne pathogen of major economic importance in pepper, and of less importance in tomato and eggplant production. As soil fumigation becomes more expensive and limited, and fungicide insensitivity of P. capsici isolates becomes more prevalent, grafting is quickly becoming an industry-favored method to control soilborne diseases. Greenhouse experiments were performed to evaluate an eggplant cultivar (Classic), two eggplant lines (EG195, EG203), a pepper line (CM334), and three pepper cultivars (Paladin, Camelot, and Red Knight) for root rot resistance to 14 P. capsici isolates. The isolates showed various degrees of virulence between pepper and eggplant in both experiments. Both eggplant and one pepper lines showed moderate resistance to the most virulent isolates tested in experiment one. The partially resistant pepper cultivar, Paladin, was significantly more susceptible than CM334 and the eggplant lines, but was still resistant to most isolates. In the second experiment, the eggplant cultivar Classic and the susceptible pepper cultivar Red Knight were both susceptible to most isolates tested, while EG203 and EG195 were resistant to most isolates. The two eggplant breeding lines, EG195 and EG203, showed moderate resistance to all isolates tested in both experiments. This is the first reported evaluation of eggplant resistance to P. capsici. Further research is warranted to test eggplant lines EG195 and EG203 for resistance to a wide range of soilborne pests and to evaluate their usefulness as P. capsici-resistant rootstocks for peppers, tomatoes, and eggplants.

15.
Phys Rev Lett ; 110(11): 115501, 2013 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-25166552

RESUMEN

The strength of shock-loaded single crystal tantalum [100] has been experimentally determined using in situ broadband x-ray Laue diffraction to measure the strain state of the compressed crystal, and elastic constants calculated from first principles. The inferred strength reaches 35 GPa at a shock pressure of 181 GPa and is in excellent agreement with a multiscale strength model [N. R. Barton et al., J. Appl. Phys. 109, 073501 (2011)], which employs a hierarchy of simulation methods over a range of length scales to calculate strength from first principles.

16.
Intern Med J ; 42(6): e136-44, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21627747

RESUMEN

BACKGROUND: Asthma guidelines advise addressing adherence at every visit, but no simple tools exist to assist clinicians in identifying key adherence-related beliefs or behaviours for individual patients. AIMS: To identify potentially modifiable beliefs and behaviours that predict electronically recorded adherence with controller therapy. METHODS: Patients aged ≥ 14 years with doctor-diagnosed asthma who were prescribed inhaled corticosteroid/long-acting ß(2)-agonist (ICS/LABA) completed questionnaires on medication beliefs/behaviours, side-effects, Morisky adherence behaviour score and Asthma Control Test (ACT), and recorded spirometry. Adherence with ICS/LABA was measured electronically over 8 weeks. Predictors of adherence were identified by univariate and multivariate analyses. RESULTS: 99/100 patients completed the study (57 female; forced expiratory volume in 1 s mean ± standard deviation 83 ± 23% predicted; ACT 19.9 ± 3.8). Mean electronically recorded adherence (n= 85) was 75% ± 25, and mean self-reported adherence was 85% ± 26%. Factor analysis of questionnaire items significantly associated with poor adherence identified seven themes: perceived necessity, safety concerns, acceptance of asthma chronicity/medication effectiveness, advice from friends/family, motivation/routine, ease of use and satisfaction with asthma management. Morisky score was moderately associated with actual adherence (r=-0.45, P < 0.0001). In regression analysis, 10 items independently predicted adherence (adjusted R(2) = 0.67; P < 0.001). Opinions of friends/family about the patient's medication use were strongly associated with poor adherence. Global concerns about ICS/LABA therapy were more predictive of poor adherence than were specific side-effects; the one-third of patients who reported experiencing side-effects from their steroid inhaler had lower adherence than others (mean 62% vs 81%; P= 0.015). CONCLUSIONS: This study identified several specific beliefs and behaviours which clinicians could use for initiating patient-centred conversations about medication adherence in asthma.


Asunto(s)
Asma/terapia , Cooperación del Paciente , Adulto , Anciano , Estudios Transversales , Manejo de la Enfermedad , Monitoreo de Drogas/métodos , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Cooperación del Paciente/estadística & datos numéricos , Análisis de Componente Principal , Estudios Prospectivos , Autoinforme
17.
Parasite Immunol ; 34(2-3): 121-9, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22098559

RESUMEN

Filarial nematode parasites, the causative agents for a spectrum of acute and chronic diseases including lymphatic filariasis and river blindness, threaten the well-being and livelihood of hundreds of millions of people in the developing regions of the world. The 2007 publication on a draft assembly of the 95-Mb genome of the human filarial parasite Brugia malayi- representing the first helminth parasite genome to be sequenced - has been followed in rapid succession by projects that have resulted in the genome sequencing of six additional filarial species, seven nonfilarial nematode parasites of animals and nearly 30 plant parasitic and free-living species. Parallel to the genomic sequencing, transcriptomic and proteomic projects have facilitated genome annotation, expanded our understanding of stage-associated gene expression and provided a first look at the role of epigenetic regulation of filarial genomes through microRNAs. The expansion in filarial genomics will also provide a significant enrichment in our knowledge of the diversity and variability in the genomes of the endosymbiotic bacterium Wolbachia leading to a better understanding of the genetic principles that govern filarial-Wolbachia mutualism. The goal here is to provide an overview of the trends and advances in filarial and Wolbachia genomics.


Asunto(s)
Filarioidea/genética , Genoma de los Helmintos/genética , Genómica/métodos , Wolbachia/genética , Animales , Filariasis/parasitología , Filarioidea/microbiología , Genoma Bacteriano/genética , Genoma Bacteriano/fisiología , Genoma de los Helmintos/fisiología , Humanos , Proteómica , ARN Pequeño no Traducido/genética , Simbiosis , Transcriptoma
18.
Clin Genet ; 81(6): 578-83, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21480868

RESUMEN

The limb-girdle muscular dystrophies (LGMDs) are a heterogenous group of diseases characterized by shoulder-girdle and pelvic muscle weakness and wasting. LGMD 2E is an autosomal recessively inherited form of the disease caused by mutations in the ß-sarcoglycan (SGCB) gene located at 4q12. In this report, we describe a patient who demonstrates non-Mendelian inheritance of a homozygous missense mutation in SGCB resulting in disease expression. A combination of single-nucleotide polymorphism (SNP) array technology and microsatellite analysis revealed the occurrence of maternal uniparental disomy (UPD) for chromosome 4 in the patient. As a consequence of segmental isodisomy at 4q12, the patient inherited two identical SGCB alleles carrying a missense mutation predicted to result in abnormal protein function. SNP array technology proved to be an elegant means to determine the most probable mechanism of UPD formation in this case, and enabled us to determine the location of recombination events along chromosome 4. In our patient, UPD likely arose from a trisomy rescue event due to maternal meiotic non-disjunction that we speculate may have been caused by abnormal recombination at the pericentromeric region. Maternal UPD 4 is a rare finding, and to our knowledge this is the first reported case of UPD in association with LGMD.


Asunto(s)
Cromosomas Humanos Par 4/genética , Distrofia Muscular de Cinturas/genética , Polimorfismo de Nucleótido Simple , Disomía Uniparental/genética , Adulto , Femenino , Humanos , Masculino , Músculo Esquelético/metabolismo , Mutación , Análisis por Matrices de Proteínas , Sarcoglicanos/genética
19.
Plant Dis ; 94(6): 697-702, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30754316

RESUMEN

A resistant pepper cultivar and nine fungicides were tested in both the field and greenhouse and their ability to limit Phytophthora crown and root rot was demonstrated. In both settings, the resistant pepper 'Paladin' and the susceptible pepper 'Red Knight' were inoculated with prepared millet seed infested with Phytophthora capsici. Foliar sprays were applied to the pepper plants on a 7-day interval in the field, and foliar sprays or drenches were applied at 7- or 14-day intervals in the greenhouse. Cv. Paladin had significantly less plant death than Red Knight. In the field, plants treated with fluopicolide or mandipropamid had significantly less plant death than the untreated control plants and, in the greenhouse, all fixed effects, including cultivar, fungicide treatment, application method, and application interval, were significant. The interactions among fungicide-cultivar, application method-cultivar, application method-fungicide, and fungicide-cultivar-application method were also significant in the greenhouse. Treatments applied as drenches provided greater control of P. capsici than those applied foliarly. Combining a resistant cultivar with a fungicide applied as a drench may help reduce the incidence of crown and root rot in pepper.

20.
Plant Dis ; 94(1): 24-30, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30754398

RESUMEN

Greenhouse and laboratory experiments were conducted to determine the virulence of four Phytophthora capsici isolates from Michigan to 31 bell and hot pepper cultivars and breeding lines. Resistance to crown and root rot was assessed following the inoculation of soilless media with P. capsici-infested millet seed. In a detached fruit assay, fruit rot resistance was evaluated following inoculation with zoospore suspensions of 1.75 × 106 zoospores/ml. The four isolates differed in virulence to pepper lines screened for crown and root rot resistance and were considered to be four different physiological races. The pepper lines CM334, NY07-8001, NY07-8006, and NY07-8007 were resistant to the isolates tested. None of the commercial cultivars were resistant to P. capsici isolate 12889, but several cultivars were resistant to the other isolates screened. The isolates varied in their ability to cause infection on the fruits of the different cultivars. Overall, pepper fruit were more susceptible to P. capsici than the roots and crowns. Management of Phytophthora crown and root rot of pepper can be improved through the use of resistant cultivars. However, since isolate virulence affects resistance, cultivar resistance will need to be utilized on a local scale accordingly.

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