3,544 research outputs found
Pupil mobility, attainment and progress in secondary school
This paper is the second of two articles arising from a study of the association between pupil mobility and attainment in national tests and examinations in an inner London borough. The first article (Strand & Demie, 2006) examined the association of pupil mobility with attainment and progress during primary school. It concluded that pupil mobility had little impact on performance in national tests at age 11, once pupils’ prior attainment at age 7 and other pupil background factors such as age, sex, special educational needs, stage of fluency in English and socio-economic disadvantage were taken into account. The present article reports the results for secondary schools (age 11-16). The results indicate that pupil mobility continues to have a significant negative association with performance in public examinations at age 16, even after including statistical controls for prior attainment at age 11 and other pupil background factors. Possible reasons for the contrasting results across school phases are explored. The implications for policy and further research are discussed
The significance of p53 codon 72 polymorphism for the development of cervical adenocarcinomas
Infection with the human papillomavirus is an important co-factor in the development of cervical carcinomas. Accordingly, HPV DNA is recognised in most of these tumours. Polymorphism of the p53 gene, codon 72, is also considered a risk factor in the development of cervical carcinoma. However, this finding is contradicted by several observers. In the present investigation, 111 cases of adenocarcinoma of the cervix collected through the Swedish Cancer Registry and 188 controls (females with normal cytology at organised gynaecological screening) were analysed with regard to p53, codon 72, polymorphism using a PCR- and SSCP-based technique. In the controls, 9% showed pro/pro, 44% pro/arg and 47% arg/arg, whereas in the invasive adenocarcinomas, the corresponding figures were 0%, 29% and 71%, respectively. The difference was statistically significant (P = 0.001). HPV DNA was identified in 86 tumours (HPV 18 in 48, HPV 16 in 31 and HPV of unknown type in 7 cases) and 25 tumours were HPV negative. The p53, codon 72, genotypes observed in HPV-positive and HPV-negative cervical adenocarcinomas were not statistically different (P = 0.690). The results indicate that women homozygotic for arg/arg in codon 72 of the p53 gene are at an increased risk for the development of cervical adenocarcinomas. However, this genetic disposition seems to be unrelated to the HPV infection. © 2001 Cancer Research Campaign http://www.bjcancer.co
Uneven distribution of HPV 16 E6 prototype and variant (L83V) oncoprotein in cervical neoplastic lesions
A previous Swedish study revealed that both prototype and variant HPV16 E6 oncoprotein, occur in about equal numbers in high-grade cervical intraepithelial neoplasia (HCIN), whereas variant HPV16 predominates in invasive cervical squamous carcinoma. Most of the malignant HPV16 variants contain a common mutation, L83V, in the E6 oncoprotein. In the present investigation, 28 HPV16 positive, invasive cervical adenocarcinomas were collected from a total number of 131 adenocarcinomas. These HPV16-positive cases were evaluated with analysis of the E6 gene, using a recently described PCR-SSCP method for identification of the specific mutation (L83V) in the E6 gene. The results obtained were correlated to findings in 103 preinvasive, HCIN, and 31 invasive cervical squamous carcinomas also infected with HPV16. The HPV16 E6 variant L83V was present in 40% of the HCIN lesions, in 54% of the invasive adenocarcinomas, in comparison to 81% of the invasive squamous carcinomas. The difference between HCIN and squamous carcinomas was statistically significant, P< 0.001, whereas the difference between HCIN and invasive adenocarcinomas was not statistically significant, P = 0.604. Prototype HPV16 and its E6 variant L83V are both prevalent in preinvasive and invasive cervical lesions in Swedish women. However, the obvious predominance of HPV16 variant in squamous carcinomas was not seen in adenocarcinomas. A single amino-acid shift in the HPV16 E6 gene appears to result in a different transforming potential in squamous and glandular cervical lesions. © 2000 Cancer Research Campaig
AGN Environments in the Sloan Digital Sky Survey I: Dependence on Type, Redshift, and Luminosity
We explore how the local environment is related to the redshift, type, and
luminosity of active galactic nuclei (AGN). Recent simulations and observations
are converging on the view that the extreme luminosity of quasars is fueled in
major mergers of gas-rich galaxies. In such a picture, quasars are expected to
be located in regions with a higher density of galaxies on small scales where
mergers are more likely to take place. However, in this picture, the activity
observed in low-luminosity AGN is due to secular processes that are less
dependent on the local galaxy density. To test this hypothesis, we compare the
local photometric galaxy density on kiloparsec scales around spectroscopic Type
I and Type II quasars to the local density around lower luminosity
spectroscopic Type I and Type II AGN. To minimize projection effects and
evolution in the photometric galaxy sample we use to characterize AGN
environments, we place our random control sample at the same redshift as our
AGN and impose a narrow redshift window around both the AGN and control
targets. We find that higher luminosity AGN have more overdense environments
compared to lower luminosity AGN on all scales out to our 2\Mpchseventy
limit. Additionally, in the range , Type II
quasars have similarly overdense environments to those of bright Type I quasars
on all scales out to our 2\Mpchseventy limit, while the environment of dimmer
Type I quasars appears to be less overdense than the environment of Type II
quasars. We see increased overdensity for Type II AGN compared to Type I AGN on
scales out to our limit of 2\Mpchseventy in overlapping redshift ranges. We
also detect marginal evidence for evolution in the number of galaxies within
2\Mpchseventy of a quasar with redshift.Comment: 30 pages, 9 figures. Major revisions made for current version. Some
content in previous version has been removed to refocus content on redshift
and type effects. This content will be deferred to later work
Precision delivery of RAS-inhibiting siRNA to KRAS driven cancer via peptide-based nanoparticles
Over 95% of pancreatic adenocarcinomas (PDACs), as well as a large fraction of other tumor types, such as colorectal adenocarcinoma, are driven by KRAS activation. However, no direct RAS inhibitors exist for cancer therapy. Furthermore, the delivery of therapeutic agents of any kind to PDAC in particular has been hindered by the extensive desmoplasia and resultant drug delivery challenges that accompanies these tumors. Small interfering RNA (siRNA) is a promising modality for anti-neoplastic therapy due to its precision and wide range of potential therapeutic targets. Unfortunately, siRNA therapy is limited by low serum half-life, vulnerability to intracellular digestion, and transient therapeutic effect. We assessed the ability of a peptide based, oligonucleotide condensing, endosomolytic nanoparticle (NP) system to deliver siRNA to KRAS-driven cancers. We show that this peptide-based NP is avidly taken up by cancer cell
Use of Non-Steroidal Anti-Inflammatory Drugs That Elevate Cardiovascular Risk: An Examination of Sales and Essential Medicines Lists in Low-, Middle-, and High-Income Countries
PMCID: PMC3570554This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Surveying the views of pupils attending supplementary schools in England
This report is the first part of a wider research project intended to evaluate the role of supplementary school in supporting pupils’ educational progress. This study reports on the first phase of this research An attitude survey to find out what young people think about mainstream and supplementary education, about the core subjects of reading and mathematics, about themselves as learners and about their reasons for attending supplementary school.. Pupil questionnaires were sent to all schools who were successful in being awarded grants from the support service. Schools were asked to administer the questionnaires to ten nominated pupils within the school, although they could give the questionnaire to more than 10 pupils if they chose. Questionnaires were returned from a total of 772 pupils attending 63 supplementary schools in four major cities in England. This is the first study to systematically explore the attitudes of pupils attending supplementary school in England and is the largest ever study of supplementary schools and their pupils
Relationship of pain and fatigue with health-related quality of life and work in patients with psoriatic arthritis on TNFi: results of a multi-national real-world study
Background/Objective: The incidence of pain and/or fatigue in people with psoriatic arthritis (PsA) is associated with reduced health-related quality of life (HRQoL) and the ability to work, despite modern advanced therapeutic approaches. This real-world, international study examined these relationships in patients with PsA treated with tumour necrosis factor inhibitors (TNFi).
Methods: Data from 13 countries were analysed. Patients with PsA and their physicians completed questionnaires capturing demographics, current therapy, current disease status, HRQoL and work status via Medical Outcomes Study 36-Item Short-Form version 2 (SF-36v2), 3-level 5-dimension EuroQoL questionnaire, Health Assessment Questionnaire Disability Index, and Work Productivity and Activity Impairment (WPAI) questionnaire.
Results: 640 patients with PsA were included who had been receiving TNFi for ≥3 months and had completed SF-36v2 bodily pain and vitality domains. Of these, 33.1%, 29.2% and 37.7% of patients reported no, moderate and severe pain, respectively, and 31.9%, 22.5% and 45.6% of patients reported low, moderate and severe fatigue, respectively. Scores across HRQoL variables and WPAI were significantly different across pain and fatigue cohorts (all p<0.0001), with HRQoL and WPAI measures considerably worse in patients with moderate to severe pain or fatigue than those with low pain or fatigue.
Conclusions: Despite treatment with biologic agents such as TNFi, data from this global study demonstrated that substantial pain and/or fatigue persist in patients with PsA and that these are significantly associated with reduced HRQoL, physical function and work productivity. These findings suggest that there is an unmet need for additional PsA therapies
Unmet needs in psoriatic arthritis patients receiving immunomodulatory therapy: results from a large multinational real-world study
Objective: There are limited data on therapy selection and switching in psoriatic arthritis (PsA). This 18 country, real-world study assessed use and switching of immunomodulatory therapy (biologic/apremilast), the extent of treatment failure and its association with reduced physical functioning, health-related quality of life (HRQoL), and work productivity and activity impairment (WPAI).
Methods: PsA patients under routine care and their treating physicians provided demographics, current therapy, reasons for switching, duration of first therapy, HRQoL, HAQ-DI, and WPAI. Current immunomodulatory therapy was determined as “failing” if, after ≥ 3 months, physician-rated disease severity had worsened, remained severe, was “unstable/deteriorating,” or they were dissatisfied with disease control and/or did not consider treatment a “success.”
Results: Included were 3714 PsA patients; 1455 (40.6%) had never received immunomodulatory therapy; 1796 (50.1%) had ever received 1 immunomodulatory therapy and 331 (9.2%) ≥ 1. Lack of efficacy with first immunomodulatory therapy was the most common reason for switching; patients whose physicians indicated “primary lack of efficacy” as the reason, switched after a mean of 9.4 months. Patients currently failing immunomodulator therapies (n = 246) had poorer HRQoL compared with treatment success (n = 1472) measured by EQ-5D-3L (0.60 vs 0.77%; P < 0.0001); SF-36 PCS (40.8% vs 46.1%; P < 0.0001) MCS (41.1% vs 45.3%; P < 0.0001). Physical functioning, activity, and work productivity were also more impaired (HAQ-DI: 0.88 vs 0.56; activity impairment: 46.7% vs 29.7%; overall work impairment: 35.4% vs 26.1%; all P < 0.0001).
Conclusions: Poor treatment response in PsA is associated with substantial negative patient impact. In cases of primary treatment failure, timely switching is needed
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