Targeted killing of colorectal cancer cell lines by a humanised IgG1 monoclonal antibody that binds to membrane-bound carcinoembryonic antigen

The distribution of carcinoembryonic antigen (CEA) in colorectal cancer (CRC) differs from that in normal colorectal tissue, being found on all borders of the cell membrane and hence enabling access to intravenous antibody, making CEA a good target for antibody-based therapy. The distinctive anti-CEA antibody, PR1A3, binds only membrane-bound CEA. Humanised PR1A3 (hPR1A3) was assessed both in vitro cytotoxicity and binding assays with colorectal cancer cell lines expressing varying levels of CEA. Human peripheral blood mononuclear cells (PBMCs) and purified natural killer (NK) cells were used as effectors. The in vitro assays demonstrated hPR1A3 CEA-specific binding and antibody-dependent and CEA-specific killing of human colorectal cancer cell lines by human PBMCs. The effect increased with increasing concentration of antibody and surface CEA, and was lost by using the parent murine IgG1 PR1A3. Killing was also blocked by antibody to the Fc-γIIIA receptor. Purified human NK cells were effective at much lower effector:target ratios than unfractionated PBMCs, indicating that NK cells were the main mediators of hPR1A3-based CEA-specific killing. The results support the development of hPR1A3 for therapy of colorectal cancer

Stres u radu sveučilišnih nastavnika: rodne i pozicijske razlike

The aim of this study was to investigate exposure to stress at work in university teachers and see if there were differences between men and women as well as between positions. The study was carried out online and included a representative sample of 1,168 teachers employed at universities in Croatia. This included all teaching positions: assistants (50 %), assistant professors (18 %), associate professors (17 %), and full professors (15 %). Fifty-seven percent of the sample were women. The participants answered a questionnaire of our own design that measured six groups of stressors: workload, material and technical conditions at work, relationships with colleagues at work, work with students, work organisation, and social recognition and status. Women reported greater stress than men. Assistant professors, associate professors, and full professors reported greater stress related to material and technical conditions of work and work organisation than assistants, who, in turn, found relationships with colleagues a greater stressor. Full professors, reported lower exposure to stress at work than associate professors, assistant professors, and assistants.Cilj rada bio je istražiti izloženost sveučilišnih nastavnika stresu u radu i ispitati postoje li razlike između muškaraca i žena te zaposlenika na različitim pozicijama u stupnju izloženosti i prirodi radnih stresora. Istraživanje je metodom on-line ankete provedeno na reprezentativnom uzorku od 1168 nastavnika zaposlenih na sveučilištima u Hrvatskoj. Obuhvaćene su bile sve znanstveno-nastavne pozicije: asistenti (51 %), docenti (19 %), izvanredni profesori (15 %) i redoviti profesori (15 %). 57 % uzorka činile su žene. Primijenjen je Upitnik izloženosti stresu u radu za sveučilišne nastavnike (ISR-SN) koji sadržava 37 čestica i mjeri šest latentnih dimenzija izvora stresa: radno opterećenje, materijalne/tehničke uvjete rada, odnose na poslu, studente, organizaciju rada i društvene uvjete rada. Žene u odnosu prema muškarcima u prosjeku izvještavaju o većoj prisutnosti izvora stresa u svom poslu. Docenti, izvanredni i redoviti profesori u prosjeku procjenjuju veću prisutnost stresora vezanih uz materijalne/tehničke uvjete rada i organizaciju rada u odnosu na asistente koji, pak, u većoj mjeri procjenjuju prisutnost stresora vezanih uz međuljudske odnose. Redoviti profesori u prosjeku izvještavaju o manjoj izloženosti stresorima u svom poslu od izvanrednih profesora, docenata i asistenata

Consumerisation in UK Higher Education Business Schools: Higher fees, greater stress and debatable outcomes

For many UK Higher Education Business Schools, the continued recruitment of UK, EU and International students is crucial for financial stability, viability and independence. Due to increasingly competitive funding models across the sector many institutional leaders and administrators are making decisions typical of highly marketised consumer environments. Thus, this paper explores, academics’ perceptions of the impact of consumerisation in UK Higher Education Business Schools. To achieve this 22 Business School academics were interviewed within three UK Higher Education institutions (HEIs) in the North of England. Participants had a minimum of three years teaching experience. Data was analysed using template analysis taking an interpretive approach. The findings indicate that academics perceived the introduction of tuition fees to have been the catalyst for students increasing demonstration of customer-like behaviour: viewing the education process as transactional, with the HEI providing a ‘paid for’ service. It is argued that these changes in UK Higher Education have created tensions between university leaders and academics, creating genuine dilemmas for those with decision-making responsibilities who must balance academic integrity and long term institutional financial viability

T-staging of rectal cancer: accuracy of 3.0 Tesla MRI compared with 1.5 Tesla

OBJECTIVES: Magnetic resonance imaging (MRI) is not accurate in discriminating T1-2 from borderline T3 rectal tumors. Higher resolution on 3 Tesla-(3T)-MRI could improve diagnostic performance for T-staging. The aim of this study was to determine whether 3T-MRI compared with 1.5 Tesla-(1.5T)-MRI improves the accuracy for the discrimination between T1-2 and borderline T3 rectal tumors and to evaluate reproducibility. METHODS: 13 patients with non-locally advanced rectal cancer underwent imaging with both 1.5T and 3T-MRI. Three readers with different expertise evaluated the images and predicted T-stage with a confidence level score. Receiver operator characteristics curves with areas under the curve (AUC) and diagnostic parameters were calculated. Inter- and intra-observer agreements were calculated with quadratic kappa-weighting. Histology was the reference standard. RESULTS: Seven patients had pT1-2 tumors and six had pT3 tumors. AUCs ranged from 0.66 to 0.87 at 1.5T vs. 0.52-0.82 at 3T. Mean overstaging rate was 43% at 1.5T and 57% at 3T (P = 0.23). Inter-observer agreement was kappa 0.50-0.71 at 1.5T vs. 0.15-0.68 at 3T. Intra-observer agreement was kappa 0.71 at 1.5T and 0.76 at 3T. CONCLUSIONS: This is the first study to compare 3T with 1.5T MRI for T-staging of rectal cancer within the same patients. Our results showed no difference between 3T and 1.5T-MRI for the distinction between T1-2 and borderline T3 tumors, regardless of expertise. The higher resolution at 3T-MRI did not aid in the distinction between desmoplasia in T1-2-tumors and tumor stranding in T3-tumors. Larger studies are needed to acknowledge these findings

Work characteristics and determinants of job satisfaction in four age groups: university employees’ point of view

Contains fulltext : 79843.pdf (publisher's version ) (Closed access)PURPOSE: To investigate (a) differences in work characteristics and (b) determinants of job satisfaction among employees in different age groups. METHODS: A cross-sectional questionnaire was filled in by 1,112 university employees, classified into four age groups. (a) Work characteristics were analysed with ANOVA while adjusting for sex and job classification. (b) Job satisfaction was regressed against job demands and job resources adapted from the Job Demands-Resources model. Results : Statistically significant differences concerning work characteristics between age groups are present, but rather small. Regression analyses revealed that negative association of the job demands workload and conflicts at work with job satisfaction faded by adding job resources. Job resources were most correlated with more job satisfaction, especially more skill discretion and more relations with colleagues. CONCLUSIONS: Skill discretion and relations with colleagues are major determinants of job satisfaction. However, attention should also be given to conflicts at work, support from supervisor and opportunities for further education, because the mean scores of these work characteristics were disappointing in almost all age groups. The latter two characteristics were found to be associated significantly to job satisfaction in older workers

Clinical impact of genomic testing in patients with suspected monogenic kidney disease

Purpose: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease. Methods: We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. Results: ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). Conclusion: In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design

Mindful networks? Navigating and negotiating life and work in academia.

In this chapter I unpack my use of social networks (and social media) as a means of being more mindful about the role of research and scholarship in the construction of my academic identity. I have found it to be a restless, shifting identity that has to be carefully and continually navigated and negotiated. On the one hand, I explain how participation in social networks has actively shaped my sense of academic community and also the scholarly relationships that contribute strongly to my academic health and wellbeing. On the other hand, I question the extent to which social networking and the use of social media in academia allow truly mindful practices to be enacted. For example, I sometimes worry that social networking for academic purposes through social media contributes to the acceleration of higher education practice – never switching off, always being connected – potentially further exacerbating academics’ levels of labour, stress and pressure. By reflecting upon and analysing my scholarly use of Twitter and Instagram I explore how this practice (usually) keeps me acting mindfully as an academic and evaluate the extent to which it enables me to engage better in the complex cognitive and emotional demands of working in higher education. Finally, I reflect upon my recent change of both role and institution, which saw me unexpectedly and temporarily suspend my regular use of social media for academic purposes.N/