3,884 research outputs found
Developing and evaluating interventions to reduce inappropriate prescribing by general practitioners of antibiotics for upper respiratory tract infections: a randomised controlled trial to compare paper-based and web-based modelling experiments
No full textBackground Much implementation research is focused on full-scale trials with little evidence of preceding modelling work. The Medical Research Council Framework for developing and evaluating complex interventions has argued for more and better theoretical and exploratory work prior to a trial as a means of improving intervention development. Intervention modelling experiments (IMEs) are a way of exploring and refining an intervention before moving to a full-scale trial. They do this by delivering key elements of the intervention in a simulation that approximates clinical practice by, for example, presenting general practitioners (GPs) with a clinical scenario about making a treatment decision. Methods The current proposal will run a full, web-based IME involving 250 GPs that will advance the methodology of IMEs by directly comparing results with an earlier paper-based IME. Moreover, the web-based IME will evaluate an intervention that can be put into a full-scale trial that aims to reduce antibiotic prescribing for upper respiratory tract infections in primary care. The study will also include a trial of email versus postal invitations to participate. Discussion More effective behaviour change interventions are needed and this study will develop one such intervention and a system to model and test future interventions. This system will be applicable to any situation in the National Health Service where behaviour needs to be modified, including interventions aimed directly at the public. Trial registration Current Controlled Trials NCT01206738
A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer
No full textThe FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region.Methods:
We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer.Results:
The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours.Conclusion:
The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer
Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers
No full textBackgroundThe MDM2 gene encodes a negative regulator of the p53 tumour suppressor protein. A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at nucleotide 309) has been reported to produce accelerated tumour formation in individuals with inherited p53 mutations. We have investigated the effect of the MDM2 SNP309 on clinical outcome in a cohort of patients with germline mutations of BRCA1.MethodsGenomic DNA was obtained for 102 healthy controls and 116 patients with established pathogenic mutations of BRCA1 and Pyrosequencing technology™ was used to determine the genotype at the MDM2 SNP309 locus.ResultsThe polymorphism was present in 52.9% of the controls (G/T in 37.3% and G/G in 15.6%) and 58.6% of the BRCA1 mutation carriers (47.4% G/T and 11.2% G/G). Incidence of malignancy in female BRCA1 carriers was not significantly higher in SNP309 carriers than in wildtype (T/T) individuals (72.7% vs. 75.6%, p = 1.00). Mean age of diagnosis of first breast cancer was 41.2 years in the SNP309 G/G genotype carriers, 38.6 years in those with the SNP309 G/T genotype and 39.0 years in wildtype subjects (p = 0.80).ConclusionWe found no evidence that the MDM2 SNP309 accelerates tumour development in carriers of known pathogenic germline mutations of BRCA1
Entanglement and quantity in quantum space - About quantum measurement (II)
No full textAs a continuation and extension of "quantity in phase space" "quantity in quantum space" is introduced. With that, the disappearing of quantum interference discussed in a previous paper [S. Durr, et al., Nature 395 (1998) 33] is explained in the same spirit as our recent papers [Ren De-Ming, Commun. Theor. Phys. (Beijing, China) 41 (2004) 685, 833].Physics, MultidisciplinarySCI(E)中国科学引文数据库(CSCD)1ARTICLE133-364
Sneutrino DM in the NMSSM with inverse seesaw mechanism
No full textIn supersymmetric theories like the Next-to-Minimal Supersymmetric Standard Model (NMSSM), the lightest neutralino with bino or singlino as its dominant component is customarily taken as dark matter (DM) candidate. Since light Higgsinos favored by naturalness can strength the couplings of the DM and thus enhance the DM-nucleon scattering rate, the tension between naturalness and DM direct detection results becomes more and more acute with the improved experimental sensitivity. In this work, we extend the NMSSM by inverse seesaw mechanism to generate neutrino mass, and show that in certain parameter space the lightest sneutrino may act as a viable DM candidate, i.e. it can annihilate by multi-channels to get correct relic density and meanwhile satisfy all experimental constraints. The most striking feature of the extension is that the DM-nucleon scattering rate can be naturally below its current experimental bounds regardless of the higgsino mass, and hence it alleviates the tension between naturalness and DM experiments. Other interesting features include that the Higgs phenomenology becomes much richer than that of the original NMSSM due to the relaxed constraints from DM physics and also due to the presence of extra neutrinos, and that the signatures of sparticles at colliders are quite different from those with neutralino as DM candidate.National Natural Science Foundation of China (NNSFC) [11575053]SCI(E)ARTICLE1
Classical mechanics and quantum mechanics
No full textThe Newton equation of motion is derived from quantum mechanics.Physics, MultidisciplinarySCI(E)中国科学引文数据库(CSCD)2ARTICLE5685-6884
Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer
No full textTamoxifen is the standard-of-care treatment for estrogen receptor-positive premenopausal breast cancer. We examined tamoxifen metabolism via blood metabolite concentrations and germline variations of CYP3A5, CYP2C9, CYP2C19 and CYP2D6 in 587 premenopausal patients (Asians, Middle Eastern Arabs, Caucasian-UK; median age 39 years) and clinical outcome in 306 patients. N-desmethyltamoxifen (DM-Tam)/(Z)-endoxifen and CYP2D6 phenotype significantly correlated across ethnicities (R2: 53%, P<10?77). CYP2C19 and CYP2C9 correlated with norendoxifen and (Z)-4-hydroxytamoxifen concentrations, respectively (P<0.001). DM-Tam was influenced by body mass index (P<0.001). Improved distant relapse-free survival (DRFS) was associated with decreasing DM-Tam/(Z)-endoxifen (P=0.036) and increasing CYP2D6 activity score (hazard ratio (HR)=0.62; 95% confidence interval (CI), 0.43–0.91; P=0.013). Low (<14?nM) compared with high (>35?nM) endoxifen concentrations were associated with shorter DRFS (univariate P=0.03; multivariate HR=1.94; 95% CI, 1.04–4.14; P=0.064). Our data indicate that endoxifen formation in premenopausal women depends on CYP2D6 irrespective of ethnicity. Low endoxifen concentration/formation and decreased CYP2D6 activity predict shorter DRFS
Policy-driven Data Sharing over Attribute-Based Encryption supporting Dual Membership
No full textAttribute-Based Encryption (ABE) plays an important role in current secure data sharing through fine-grained customizable policies. However, the existing ABE schemes only support simple predicates, = and ≠, but cannot express a more general membership predicates, ∈ and ∉, in policies. The low expressivity of ABE will enlarge the ciphertext storage and reduce the communication efficiency. To overcome this problem, we propose an ABE supporting Dual Membership (DM-ABE). The core problem for implementing this scheme is how to use cryptographic methods to decide the membership between the verified element and the given set. In order to solve this problem, we design a cryptographic algorithm, called Secure Decision of Membership (SDM), based on aggregation functions. In this algorithm, any set can be aggregated into one cryptographic element, and the verified element and the given set can be converted into another cryptographic element in decision process. The membership between them can be decided by the above two cryptographic elements. Furthermore, we construct the DM-ABE by using SDM. Because of the good expressivity of our DM-ABE, we further propose a novel cryptographic data sharing framework by integrating DM-ABE and attribute-based access control to provide fine-grained access control and security protection for private data. In the security proof of DM-ABE, we prove that the DM-ABE satisfies the semantic security against chosen-plaintext attacks under the DBDHE assumption in the standard model through a unified way, considering both two encryption methods for ∈ and ∉ at the same time. Finally, we analyze our scheme in terms of time and space complexity, and compare it with some existing schemes. The results show that our DM-ABE has a better expressive ability on the boolean logic of general membership predicates, ∈ and ∉.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Cyber Securit
Apoptosis, ageing and cancer susceptibility
No full textWe have previously shown that peripheral blood lymphocytes (PBL) from individuals carrying a germline TP53 mutation show a dramatically reduced apoptotic response to radiation. As part of a study of this phenomenon, we also investigated apoptotic response in a series of breast cancer patients lacking TP53 mutations and in a control group of individuals without cancer. There was a significant reduction in mean apoptotic response with increasing age in all groups. These findings are consistent with a number of studies in rodents, which have demonstrated a reduction in DNA damage-induced apoptosis with increasing age. In addition, after adjusting for age, breast cancer patients showed significantly reduced apoptotic responses compared with normal controls (P=0.002). The odds ratio for breast cancer in women with an apoptotic response of <35%, compared with women with a response of >49%, was 6.42 (95% CI 1.68-24.6). The data further support the hypothesis that a reduction in apoptotic response to DNA damage with increasing age may play a significant role in the age-related increase in cancer
Obesity and the outcome of young breast cancer patients in the UK: the POSH study
No full textBackgroundObese breast cancer patients have a poorer prognosis than non-obese patients. We examined data from a large prospective cohort study to explore the associations of obesity with tumour pathology, treatment and outcome in young British breast cancer patients receiving modern oncological treatments.Patients and methodsA total of 2956 patients aged ?40 at breast cancer diagnosis were recruited from 126 UK hospitals from 2001 to 2007. Height and weight were measured at registration. Tumour pathology and treatment details were collected. Follow-up data were collected at 6, 12 months, and annually.ResultsA total of 2843 eligible patients (96.2%) had a body mass index (BMI) recorded: 1526 (53.7%) were under/healthy-weight (U/H, BMI <25 kg/m2), 784 (27.6%) were overweight (ov, BMI ?25 to <30), and 533 (18.7%) were obese (ob, BMI ?30). The median tumour size was significantly higher in obese and overweight patients than U/H patients (Ob 26 mm versus U/H 20 mm, P < 0.001; Ov 24 mm versus U/H 20 mm, P < 0.001). Obese and overweight patients had significantly more grade 3 tumours (63.9% versus 59.0%, P = 0.048; Ov 63.6% versus U/H 59.0% P = 0.034) and node-positive tumours (Ob 54.6% versus U/H 49.0%, P = 0.027; Ov 54.2% versus U/H 49%, P = 0.019) than U/H patients. Obese patients had more ER/PR/HER2-negative tumours than healthy-weight patients (25.0% versus 18.3%, P = 0.001). Eight-year overall survival (OS) and distant disease-free interval (DDFI) were significantly lower in obese patients than healthy-weight patients [OS: hazard ratio (HR) 1.65, P < 0.001; DDFI: HR 1.44, P < 0.001]. Multivariable analyses adjusting for tumour grade, size, nodal, and HER2 status indicated that obesity was a significant independent predictor of OS and DDFI in patients with ER-positive disease.ConclusionsYoung obese breast cancer patients present with adverse tumour characteristics. Despite adjustment for this, obesity still independently predicts DDFI and OS
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