Serum CEA and CA 15-3 as prognostic factors in primary breast cancer

In the present study, we investigated the association of the serum levels of the tumour markers carcinoembryonic antigen and cancer antigen 15-3 with disease free survival and death from disease in 1046 women with breast cancer without metastases at the time of primary diagnosis in relation to age and the established prognostic factors tumour size, lymph node status, histological grading and hormone receptor status. We found that elevated pre-operative serum marker values were correlated with early relapse (cancer antigen 15-3; P=0.0003) and death from disease (carcinoembryonic antigen, cancer antigen 15-3; P=0.0001 both) in univariate analyses. By comparing pre- and post-operative values we found a decline in values post-surgery. In those patients where marker levels of carcinoembryonic antigen decreased more than 33%, a significantly higher risk for relapse and death from disease (both P=0.0001) in univariate analyses was observed. In multivariate analysis this decrease of carcinoembryonic antigen proved to be an independent prognostic factor. The results for cancer antigen 15-3 were comparable to carcinoembryonic antigen in univariate analyses but showed no significance in multivariate analysis. In this study the post-operative decrease of the serum tumour marker carcinoembryonic antigen was a strong independent prognostic factor for disease free survival and death from disease in breast cancer patients

Work–Family Conflict and Job Outcomes Among Prison Officers in Ghana: A Test of Mediation and Moderation Processes

This study examines the mediating effect of job stress and the moderating effect of job autonomy on the relationship between work-to-family conflict (WFC) and job satisfaction and organizational commitment. It uses cross-sectional data from 1062 prison officers sampled from 31 prison establishments in Ghana. The results of structural equation modelling (SEM) analysis showed that WFC was negatively associated with job satisfaction and organizational commitment. Job stress significantly mediated the influence of WFC on job satisfaction and organizational commitment. The negative influence of WFC on job satisfaction and organizational commitment was less for prison officers with higher levels of job autonomy than for those with lower levels of autonomy. These findings suggest the need for correctional organizations to adopt family-friendly measures that facilitate officers’ ability to integrate their work and family responsibilities

Factors influencing the participation of gastroenterologists and hepatologists in clinical research

<p>Abstract</p> <p>Background</p> <p>Although clinical research is integral to the advancement of medical knowledge, physicians face a variety of obstacles to their participation as investigators in clinical trials. We examined factors that influence the participation of gastroenterologists and hepatologists in clinical research.</p> <p>Methods</p> <p>We surveyed 1050 members of the American Association for the Study of Liver Diseases regarding their participation in clinical research. We compared the survey responses by specialty and level of clinical trial experience.</p> <p>Results</p> <p>A majority of the respondents (71.6%) reported involvement in research activities. Factors most influential in clinical trial participation included funding and compensation (88.3%) and intellectual pursuit (87.8%). Barriers to participation were similar between gastroenterologists (n = 160) and hepatologists (n = 189) and between highly experienced (n = 62) and less experienced (n = 159) clinical researchers. These barriers included uncompensated research costs and lack of specialized support. Industry marketing was a greater influence among respondents with less trial experience, compared to those with extensive experience (15.7% vs 1.6%; <it>P </it>< .01). Hepatologists and respondents with extensive clinical trial experience tended to be more interested in phase 1 and 2 studies, whereas gastroenterologists and less experienced investigators were more interested in phase 4 studies.</p> <p>Conclusion</p> <p>This study suggests that the greatest barrier to participation in clinical research is lack of adequate resources. Respondents also favored industry-sponsored research with less complex trial protocols and studies of relatively short duration.</p

Comparison of contrast enhanced three dimensional echocardiography with MIBI gated SPECT for the evaluation of left ventricular function

Background. In clinical practice and in clinical trials, echocardiography and scintigraphy are used the most for the evaluation of global left ejection fraction (LVEF) and left ventricular (LV) volumes. Actually, poor quality imaging and geometrical assumptions are the main limitations of LVEF measured by echocardiography. Contrast agents and 3D echocardiography are new methods that may alleviate these potential limitations. Methods. Therefore we sought to examine the accuracy of contrast 3D echocardiography for the evaluation of LV volumes and LVEF relative to MIBI gated SPECT as an independent reference. In 43 patients addressed for chest pain, contrast 3D echocardiography (RT3DE) and MIBI gated SPECT were prospectively performed on the same day. The accuracy and the variability of LV volumes and LVEF measurements were evaluated. Results. Due to good endocardial delineation, LV volumes and LVEF measurements by contrast RT3DE were feasible in 99% of the patients. The mean LV end-diastolic volume (LVEDV) of the group by scintigraphy was 143 65 mL and was underestimated by triplane contrast RT3DE (128 60 mL; p < 0.001) and less by full-volume contrast RT3DE (132 62 mL; p < 0.001). Limits of agreement with scintigraphy were similar for triplane andfull-volume, modalities with the best results for full-volume. Results were similar for calculation of LV end-systolic volume (LVESV). The mean LVEF was 44 16% with scintigraphy and was not significantly different with both triplane contrast RT3DE (45 15%) and full-volume contrast RT3DE (45 15%). There was an excellent correlation between two different observers for LVEDV, LVESV and LVEF measurements and inter observer agreement was also good for both contrast RT3DE techniques. Conclusion. Contrast RT3DE allows an accurate assessment of LVEF compared to the LVEF measured by SPECT, and shows low variability between observers. Although RT3DE triplane provides accurate evaluation of left ventricular function, RT3DE full-volume is superior to triplane modality in patients with suspected coronary artery disease. © 2009 Cosyns et al; licensee BioMed Central Ltd.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR): review of phenotype associated with KIF11 mutations

Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR) (MIM No.152950) is a rare autosomal dominant condition for which a causative gene has recently been identified. Mutations in the kinesin family member 11 (KIF11) gene have now been described in 16 families worldwide. This is a review of the condition based on the clinical features of 37 individuals from 22 families. This report includes nine previously unreported families and additional information for some of those reported previously. The condition arose de novo in 8/20 families (40%). The parental results were not available for two probands. The mutations were varied and include missense, nonsense, frameshift, and splice site and are distributed evenly throughout the KIF11 gene. In our cohort, 86% had microcephaly, 78% had an ocular abnormality consistent with the diagnosis, 46% had lymphoedema, 73% had mild-moderate learning difficulties, 8% had epilepsy, and 8% had a cardiac anomaly. We identified three individuals with KIF11 mutations but no clinical features of MCLMR demonstrating reduced penetrance. The variable expression of the phenotype and the presence of mildly affected individuals indicates that the prevalence may be higher than expected, and we would therefore recommend a low threshold for genetic testing

Recruiting a New Substrate for Triacylglycerol Synthesis in Plants: The Monoacylglycerol Acyltransferase Pathway

BACKGROUND: Monoacylglycerol acyltransferases (MGATs) are predominantly associated with lipid absorption and resynthesis in the animal intestine where they catalyse the first step in the monoacylglycerol (MAG) pathway by acylating MAG to form diacylglycerol (DAG). Typical plant triacylglycerol (TAG) biosynthesis routes such as the Kennedy pathway do not include an MGAT step. Rather, DAG and TAG are synthesised de novo from glycerol-3-phosphate (G-3-P) by a series of three subsequent acylation reactions although a complex interplay with membrane lipids exists. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that heterologous expression of a mouse MGAT acyltransferase in Nicotiana benthamiana significantly increases TAG accumulation in vegetative tissues despite the low levels of endogenous MAG substrate available. In addition, DAG produced by this acyltransferase can serve as a substrate for both native and coexpressed diacylglycerol acyltransferases (DGAT). Finally, we show that the Arabidopsis thaliana GPAT4 acyltransferase can produce MAG in Saccharomyces cerevisiae using oleoyl-CoA as the acyl-donor. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the concept of a new method of increasing oil content in vegetative tissues by using MAG as a substrate for TAG biosynthesis. Based on in vitro yeast assays and expression results in N. benthamiana, we propose that co-expression of a MAG synthesising enzyme such as A. thaliana GPAT4 and a MGAT or bifunctional M/DGAT can result in DAG and TAG synthesis from G-3-P via a route that is independent and complementary to the endogenous Kennedy pathway and other TAG synthesis routes

The E3 ligase HUWE1 inhibition as a therapeutic strategy to target MYC in multiple myeloma

Proteasome inhibitors have provided a significant advance in the treatment of multiple myeloma (MM). Consequently, there is increasing interest in developing strategies to target E3 ligases, de-ubiquitinases, and/or ubiquitin receptors within the ubiquitin proteasome pathway, with an aim to achieve more specificity and reduced side-effects. Previous studies have shown a role for the E3 ligase HUWE1 in modulating c-MYC, an oncogene frequently dysregulated in MM. Here we investigated HUWE1 in MM. We identified elevated expression of HUWE1 in MM compared with normal cells. Small molecule-mediated inhibition of HUWE1 resulted in growth arrest of MM cell lines without significantly effecting the growth of normal bone marrow cells, suggesting a favorable therapeutic index. Studies using a HUWE1 knockdown model showed similar growth inhibition. HUWE1 expression positively correlated with MYC expression in MM bone marrow cells and correspondingly, genetic knockdown and biochemical inhibition of HUWE1 reduced MYC expression in MM cell lines. Proteomic identification of HUWE1 substrates revealed a strong association of HUWE1 with metabolic processes in MM cells. Intracellular glutamine levels are decreased in the absence of HUWE1 and may contribute to MYC degradation. Finally, HUWE1 depletion in combination with lenalidomide resulted in synergistic anti-MM activity in both in vitro and in vivo models. Taken together, our data demonstrate an important role of HUWE1 in MM cell growth and provides preclinical rationale for therapeutic strategies targeting HUWE1 in MM

Clinicopathologic study associated with long-term survival in Japanese patients with node-negative breast cancer

This study was undertaken to determine the absolute and relative value of blood vessel invasion (BVI) using both factor VIII-related antigen and elastica van Gieson staining, proliferating cell nuclear antigen (PCNA), p53, c- erb B-2, and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer. Two hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including PCNA, p53, c- erb B-2 using permanent-section immunohistochemistry, clinical tumour size (T), histological grade (HG), mitotic index (MI), tumour necrosis (TN), lymphatic vessel invasion (LVI) and BVI, followed for a median of 10 years (range 1–20). Twenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that BVI, PCNA, T, HG, MI, p53, c- erb B-2 and LVI were significantly predictive of 20-year RFS or OS. Multivariate analysis showed that BVI (P = 0.0159, P = 0.0368), proliferating cell nuclear antigen (PCNA) (P = 0.0165, P = 0.0001), and T (P = 0.0190, P = 0.0399) were significantly independent prognostic factors for RFS or OS respectively. BVI, PCNA and T were independent prognostic indicators for RFS or OS in Japanese patients with node-negative breast cancer and are useful in selecting high-risk patients who may be eligible to receive strong adjuvant therapies. © 2000 Cancer Research Campaig

Structural and non-coding variants increase the diagnostic yield of clinical whole genome sequencing for rare diseases

BACKGROUND: Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, the diagnostic yields of many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25–30%. This is in part because although entire genomes are sequenced, analysis is often confined to in silico gene panels or coding regions of the genome. METHODS: We undertook WGS on a cohort of 122 unrelated rare disease patients and their relatives (300 genomes) who had been pre-screened by gene panels or arrays. Patients were recruited from a broad spectrum of clinical specialties. We applied a bioinformatics pipeline that would allow comprehensive analysis of all variant types. We combined established bioinformatics tools for phenotypic and genomic analysis with our novel algorithms (SVRare, ALTSPLICE and GREEN-DB) to detect and annotate structural, splice site and non-coding variants. RESULTS: Our diagnostic yield was 43/122 cases (35%), although 47/122 cases (39%) were considered solved when considering novel candidate genes with supporting functional data into account. Structural, splice site and deep intronic variants contributed to 20/47 (43%) of our solved cases. Five genes that are novel, or were novel at the time of discovery, were identified, whilst a further three genes are putative novel disease genes with evidence of causality. We identified variants of uncertain significance in a further fourteen candidate genes. The phenotypic spectrum associated with RMND1 was expanded to include polymicrogyria. Two patients with secondary findings in FBN1 and KCNQ1 were confirmed to have previously unidentified Marfan and long QT syndromes, respectively, and were referred for further clinical interventions. Clinical diagnoses were changed in six patients and treatment adjustments made for eight individuals, which for five patients was considered life-saving. CONCLUSIONS: Genome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing

Modelling the Sociocultural Contexts of Science Education: The Teachers’ Perspective

publication-status: Publishedtypes: ArticleA growing body of research argues that teachers’ beliefs and practices should be studied within the sociocultural contexts of their work because the relationship between their beliefs and practices is both complex and context-dependent. There is a need for further research in this area in understudied contexts such as developing countries, in order to promote effective education in schools and the professional development of teachers. This paper argues that if this ‘black box’ of sociocultural contexts in which science teachers are embedded is better understood, it may be possible to identify specific aspects of these contexts related to educational organizations that act as either supports or barriers to pedagogical reform or to implementing innovations in science education. Consequently, the main purpose of this study is to explore the sociocultural contexts of ten Egyptian science teachers and to what extent these sociocultural contexts help in understanding teachers’ pedagogical beliefs and practices. This paper, by utilizing a multi-grounded theory approach and qualitative methods, reveals a variety of sociocultural contexts that are related to teachers’ pedagogical beliefs and practices