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1.
J Asthma ; 55(9): 1018-1027, 2018 09.
Article in English | MEDLINE | ID: mdl-29064746

ABSTRACT

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.


Subject(s)
Asthma/therapy , Mobile Applications , Self-Management/methods , Software Design , Adolescent , Female , Humans , Male , Patient Satisfaction , Patients/psychology , Pharmacists/psychology , Research Design , Respiratory Therapy/methods , Telemedicine , Young Adult
2.
Phys Rev Lett ; 119(5): 055001, 2017 Aug 04.
Article in English | MEDLINE | ID: mdl-28949745

ABSTRACT

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.

3.
Br J Cancer ; 113(1): 57-63, 2015 Jun 30.
Article in English | MEDLINE | ID: mdl-26035700

ABSTRACT

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.


Subject(s)
Genes, myc , Neuroblastoma/pathology , Nuclear Proteins/physiology , Oncogene Proteins/physiology , Cell Differentiation , Child , Cohort Studies , Humans , N-Myc Proto-Oncogene Protein , Neuroblastoma/genetics , Nuclear Proteins/genetics , Oncogene Proteins/genetics , Prognosis
4.
Allergy ; 69(3): 372-9, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24444382

ABSTRACT

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.


Subject(s)
Adrenal Cortex Hormones/adverse effects , Anti-Asthmatic Agents/adverse effects , Asthma/epidemiology , Administration, Inhalation , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Anti-Asthmatic Agents/administration & dosage , Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Female , Health Surveys , Humans , Male , Middle Aged , Quality of Life , Reproducibility of Results , Risk Factors , Surveys and Questionnaires
5.
Mol Pharm ; 11(11): 3930-7, 2014 Nov 03.
Article in English | MEDLINE | ID: mdl-24992368

ABSTRACT

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.


Subject(s)
Acetates/pharmacology , Copper Radioisotopes/chemistry , Gallium Radioisotopes/chemistry , Gastrins/chemistry , Heterocyclic Compounds, 1-Ring/pharmacology , Heterocyclic Compounds/pharmacology , Indium Radioisotopes/chemistry , Animals , Cell Line, Tumor , Chelating Agents/chemistry , Female , Humans , Inhibitory Concentration 50 , Mice , Mice, SCID , Multimodal Imaging , Neoplasm Transplantation , Peptides/chemistry , Positron-Emission Tomography , Radiopharmaceuticals/chemistry , Receptor, Cholecystokinin B/metabolism , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed
6.
Acta Paediatr ; 103(10): e439-43, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24919409

ABSTRACT

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.


Subject(s)
Arginase/genetics , Bronchopulmonary Dysplasia/complications , Hypertension, Pulmonary/genetics , Case-Control Studies , Female , Humans , Infant, Newborn , Infant, Premature , Male , Polymorphism, Single Nucleotide
7.
Leukemia ; 38(4): 720-728, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38360863

ABSTRACT

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.


Subject(s)
Burkitt Lymphoma , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Child , Humans , Young Adult , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Prognosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Recurrence , Risk Assessment , Disease-Free Survival
8.
Phys Rev Lett ; 110(11): 115501, 2013 Mar 15.
Article in English | MEDLINE | ID: mdl-25166552

ABSTRACT

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.

9.
Plant Dis ; 97(8): 1037-1041, 2013 Aug.
Article in English | MEDLINE | ID: mdl-30722468

ABSTRACT

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.

10.
Clin Genet ; 81(6): 578-83, 2012 Jun.
Article in English | MEDLINE | ID: mdl-21480868

ABSTRACT

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.


Subject(s)
Chromosomes, Human, Pair 4/genetics , Muscular Dystrophies, Limb-Girdle/genetics , Polymorphism, Single Nucleotide , Uniparental Disomy/genetics , Adult , Female , Humans , Male , Muscle, Skeletal/metabolism , Mutation , Protein Array Analysis , Sarcoglycans/genetics
11.
Parasite Immunol ; 34(2-3): 121-9, 2012.
Article in English | MEDLINE | ID: mdl-22098559

ABSTRACT

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.


Subject(s)
Filarioidea/genetics , Genome, Helminth/genetics , Genomics/methods , Wolbachia/genetics , Animals , Filariasis/parasitology , Filarioidea/microbiology , Genome, Bacterial/genetics , Genome, Bacterial/physiology , Genome, Helminth/physiology , Humans , Proteomics , RNA, Small Untranslated/genetics , Symbiosis , Transcriptome
12.
Intern Med J ; 42(6): e136-44, 2012 Jun.
Article in English | MEDLINE | ID: mdl-21627747

ABSTRACT

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.


Subject(s)
Asthma/therapy , Patient Compliance , Adult , Aged , Cross-Sectional Studies , Disease Management , Drug Monitoring/methods , Factor Analysis, Statistical , Female , Humans , Male , Middle Aged , Multivariate Analysis , Patient Compliance/statistics & numerical data , Principal Component Analysis , Prospective Studies , Self Report
13.
Nat Commun ; 12(1): 334, 2021 Jan 12.
Article in English | MEDLINE | ID: mdl-33436570

ABSTRACT

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.

14.
Plant Dis ; 94(6): 697-702, 2010 Jun.
Article in English | MEDLINE | ID: mdl-30754316

ABSTRACT

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.

15.
Plant Dis ; 94(1): 24-30, 2010 Jan.
Article in English | MEDLINE | ID: mdl-30754398

ABSTRACT

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.

16.
Respir Med ; 175: 106154, 2020 12.
Article in English | MEDLINE | ID: mdl-33190085

ABSTRACT

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.


Subject(s)
Asthma/drug therapy , Asthma/psychology , Budesonide, Formoterol Fumarate Drug Combination/administration & dosage , Nebulizers and Vaporizers , Qualitative Research , Administration, Inhalation , Adolescent , Adult , Aged , Attitude to Health , Female , Humans , Male , Medication Adherence , Middle Aged , Patient Preference , Physician-Patient Relations , Randomized Controlled Trials as Topic , Severity of Illness Index , Young Adult
18.
Cancer Res ; 59(18): 4725-31, 1999 Sep 15.
Article in English | MEDLINE | ID: mdl-10493532

ABSTRACT

Transforming growth factor betas (TGF-betas) are a growth factor family with negative autocrine growth functions for most epithelial cells including colon carcinoma cell lines. Both type I (RI) and type II (RII) transmembrane TGF-beta receptors have been shown to be indispensable for TGF-beta-mediated cell growth regulation. Previous studies using different model systems have shown that both overexpression of TGF-beta1 and transfection of antisense TGF-beta1 to reduce TGF-beta1 expression could lead to increased tumorigenicity. These results are seemingly contradictory and suggest that effects of TGF-beta modulation on malignant properties of cancer cells may be contextual. This study addresses this issue using human colon carcinoma cells (CBS and FET) to determine the effects of modulation of the various components of the TGF-beta system on in vitro and in vivo growth properties in two independent isogenic models of colon carcinoma. Cells were stably transfected with a tetracycline-repressible RII expression vector (CBS4-RII), a tetracycline-repressible expression vector containing a truncated RII cDNA lacking the serine/threonine kinase domain (CBS4-deltaRII and FET6-deltaRII), or with a vector containing the TGF-beta1 cDNA (CBS4-beta1S and FET-beta1S). Expression of the truncated RII reduced TGF-beta sensitivity, whereas overexpression of RII increased TGF-beta sensitivity. TGF-beta overexpression did not affect TGF-beta response. In vivo tumorigenicity assays revealed that CBS4-RII cells had lower tumorigenicity than control cells, whereas CBS4-deltaRII and CBS4-beta1S had higher tumorigenicity than controls. The CBS4 cells are poorly tumorigenic in athymic mice, and the wild-type FET6 cells are nontumorigenic. FET6-deltaRII cells formed rapidly growing tumors, and FET-beta1S cells also formed tumors. These data illustrate the paradoxical tumor-promoting and -suppressing effects of TGF-beta signaling activity in two isogenic model systems from human colon carcinomas, thus demonstrating that the effects of modulation of TGF-beta expression or TGF-beta signaling capability affects malignancy in a contextual manner.


Subject(s)
Colonic Neoplasms/pathology , Transforming Growth Factor beta/physiology , Animals , Cell Division/drug effects , Culture Media, Conditioned , Genes, Reporter , Humans , Luciferases/genetics , Mice , Mice, Nude , Receptors, Transforming Growth Factor beta/physiology , Recombinant Proteins/metabolism , Time Factors , Transfection , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/toxicity , Transplantation, Heterologous , Tumor Cells, Cultured , beta-Galactosidase/genetics
19.
Sci Rep ; 6: 24211, 2016 Apr 13.
Article in English | MEDLINE | ID: mdl-27071341

ABSTRACT

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.

20.
Nat Commun ; 7: ncomms11899, 2016 06 13.
Article in English | MEDLINE | ID: mdl-27291065

ABSTRACT

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.

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