Het Effect van de Kanker Nazorg Wijzer* op Werkgerelateerde Problematiek en Kwaliteit van Leven bij Werkende Ex-Kankerpatiënten

Doordat kanker vaker in een vroeg stadium wordt ontdekt en de behandelingen effectiever zijn, is de kans om te overleven toegenomen. Om ex-kankerpatiënten te kunnen begeleiden na hun ziekte is de Kanker Nazorg Wijzer (KNW) ontwikkeld: een online interventie voor ex-kankerpatiënten ter ondersteuning van ervaren problemen op diverse gebieden waaronder werkhervatting. De KNW bestaat uit modules met informatie, advies, training en feedback-op-maat voor die betreffende probleemgebieden. In het huidige onderzoek stond het effect van de KNW op werkgerelateerde problematiek bij werkende ex-kankerpatiënten centraal en werd ook het effect op kwaliteit van leven gemeten. Verwacht werd dat na zes maanden gebruik van de KNW het aantal werkzame uren (werkhervatting), de werktevredenheid en kwaliteit van leven bij de gebruikers (interventiegroep) meer is toegenomen dan bij de niet-gebruikers (controlegroep) en dat de problemen op het werk en de onvervulde behoefte aan werkgerelateerde informatie meer is afgenomen. Additief werd verondersteld dat, binnen de interventiegroep, de respondenten die specifiek de werkmodule hadden gebruikt een groter verschil laten zien tussen de voor- en nameting met betrekking tot de werkgerelateerde problematiek. Op basis van voorgaand onderzoek zijn sekse, leeftijd, opleiding en actieve coping meegenomen als confounders evenals de voormetingscores van de afhankelijke variabelen. Het betreft een gerandomiseerd experiment naar de effecten van de KNW. Respondenten zijn geworven bij 22 Nederlandse ziekenhuizen en werden random toegewezen aan de interventiegroep of controlegroep. Voor de effectmeting is alleen de data van werkende ex-kankerpatiënten gebruikt. Effecten werden getoetst met multiple regressie analyses waarbij werd gecorrigeerd voor de genoemde confouders. In de interventiegroep (N = 245) waren 156 werkende ex-kankerpatiënten (85.3% vrouw, leeftijd M = 50.7) en in de controlegroep (N = 236) waren dit er 134 (85.1% vrouw, leeftijd M = 51.2). De MRA gaf na correctie van de voormetingscores en confounders aan dat het gebruik van de KNW zorgde voor een significante verbetering van kwaliteit van leven op de subschalen fysiek functioneren (p = 0.005), emotioneel functioneren (p = 0.026), sociaal functioneren (p = 0.002) en vermoeidheid (p = 0.021). De MRA gaf geen significant effect van het gebruik van de KNW op de werkgerelateerde problematiek. Additief gaf een vergelijking binnen de interventiegroep tussen de gebruikers van de werkmodule (N = 25) en de niet gebruikers (N = 131) aan dat het aantal gewerkte uren significant meer was toegenomen onder de gebruikers (t (68) = 1.680, p = 0.049).

De Kanker Nazorgwijzer: Verschillen in gebruik en effect op Depressieve / Angst Klachten en Onvervulde Behoeften

Het doel van het uitgevoerde onderzoek was om te bekijken of geslacht, angst en depressie (zoals gemeten met de HADS) kunnen fungeren als voorspellers van het gebruik van een e-health interventie voor ex-kankerpatiënten. Daarnaast zijn angst en depressie als afhankelijke variabele gebruikt om te bekijken of de Kanker Nazorg Wijzer effect had op het verminderen hiervan, evenals op de mate van onvoldane behoeften (zoals gemeten met de CaSUN) die ex-kankerpatiënten ervaren. Hiertoe werd data verzameld van 467 proefpersonen die onder werden verdeeld in een interventie en een controlegroep. Beide groepen kregen op twee momenten (baseline en opnieuw na 6 maanden) een vragenlijst waarin onder andere de HADS (Hospital Anxiety Depression Scale) en de CaSUN (Cancer Survivors Unmet Needs) werd afgenomen. Er blijkt geen significant, ofwel een zeer klein verband te bestaan tussen de mate van ervaren angst of depressie en het gebruik van de interventie. Er is bij het gebruik van de interventie geen significant verschil gevonden tussen de seksen. De interventie als geheel had een positief effect op de ervaren angst en depressie, de hoeveelheid gevolgde modulen versterkt dit effect niet. Op het gebied van de onvoldane behoeften zijn de verschillen tussen de controle en de interventiegroep te klein om significant te zijn. Door de hoge correlatie tussen modulegebruik onderling, en de vastgestelde afgenomen klachten van depressie en angst kan er gezegd worden dat de KNW tegemoet lijkt te komen aan een behoefte van overlevenden van kanker en dat zij een positief effect had op de klachten van angst en depressie die veel voorkomen onder ex-kankerpatiënten.

Ex vivo investigation of novel wound healing therapies and development of a 3-D human skin equivalent wound model

It has previously been found that complexes comprised of vitronectin and growth factors (VN:GF) enhance keratinocyte protein synthesis and migration. More specifically, these complexes have been shown to significantly enhance the migration of dermal keratinocytes derived from human skin. In view of this, it was thought that these complexes may hold potential as a novel therapy for healing chronic wounds. However, there was no evidence indicating that the VN:GF complexes would retain their effect on keratinocytes in the presence of chronic wound fluid. The studies in this thesis demonstrate for the first time that the VN:GF complexes not only stimulate proliferation and migration of keratinocytes, but also these effects are maintained in the presence of chronic wound fluid in a 2-dimensional (2-D) cell culture model. Whilst the 2-D culture system provided insights into how the cells might respond to the VN:GF complexes, this investigative approach is not ideal as skin is a 3-dimensional (3-D) tissue. In view of this, a 3-D human skin equivalent (HSE) model, which reflects more closely the in vivo environment, was used to test the VN:GF complexes on epidermopoiesis. These studies revealed that the VN:GF complexes enable keratinocytes to migrate, proliferate and differentiate on a de-epidermalised dermis (DED), ultimately forming a fully stratified epidermis. In addition, fibroblasts were seeded on DED and shown to migrate into the DED in the presence of the VN:GF complexes and hyaluronic acid, another important biological factor in the wound healing cascade. This HSE model was then further developed to enable studies examining the potential of the VN:GF complexes in epidermal wound healing. Specifically, a reproducible partial-thickness HSE wound model was created in fully-defined media and monitored as it healed. In this situation, the VN:GF complexes were shown to significantly enhance keratinocyte migration and proliferation, as well as differentiation. This model was also subsequently utilized to assess the wound healing potential of a synthetic fibrin-like gel that had previously been demonstrated to bind growth factors. Of note, keratinocyte re-epitheliasation was shown to be markedly improved in the presence of this 3-D matrix, highlighting its future potential for use as a delivery vehicle for the VN:GF complexes. Furthermore, this synthetic fibrin-like gel was injected into a 4 mm diameter full-thickness wound created in the HSE, both keratinocytes and fibroblasts were shown to migrate into this gel, as revealed by immunofluorescence. Interestingly, keratinocyte migration into this matrix was found to be dependent upon the presence of the fibroblasts. Taken together, these data indicate that reproducible wounds, as created in the HSEs, provide a relevant ex vivo tool to assess potential wound healing therapies. Moreover, the models will decrease our reliance on animals for scientific experimentation. Additionally, it is clear that these models will significantly assist in the development of novel treatments, such as the VN:GF complexes and the synthetic fibrin-like gel described herein, ultimately facilitating their clinical trial in the treatment of chronic wounds.

Practice as method : the ex/centric fixations project

In the past decade, scholars have proposed a range of terms to describe the relationship between practice and research in the creative arts, including increasingly nuanced definitions of practice-based research, practice-led research and practice-as-research. In this paper, I consider the efficacy of creative practice as method. I use the example of The Ex/Centric Fixations Project – a project in which I have embedded creative practice in a research project, rather than embedding research in a creative project. The Ex/Centric Fixations project investigates the way spectators interpret human experiences – especially human experiences of difference, marginalisation or discrimination – depicted onstage. In particular, it investigates the way postmodern performance writing strategies, and the presence of performing bodied to which the experience depicted can be attached, impacts on interpretations. It is part of a broader research project which examines the performativity of spectatorship, and intervenes in emergent debates about performance, ethics and spectatorship in the context of debate about whether live performance is a privileged site for the emergence of an ethical face-to-face encounter with the Other. Using the metaphor of the Mobius strip, I examines the way practice – as a method, rather than an output – has informed, influenced and problematised the broader research project.

Comparison of Kenz Lifecorder EX and ActiGraph accelerometers in 10-yr-old children

A new accelerometer, the Kenz Lifecorder EX (LC; Suzuken Co. Ltd, Nagoya, Japan), offers promise as a feasible monitor alternative to the commonly used Actigraph (AG: Actigraph LLC, Fort Walton Beach, FL). Purpose: This study compared the LC and AG accelerometers and the Yamax SW-200 pedometer (DW) under free-living conditions with regard to children's steps taken and time in light-intensity physical activity (PA) and moderate to vigorous PA (MVPA). Methods: Participants (N = 31, age = 10.2 ± 0.4 yr) wore LC, AG, and DW monitors from arrival at school (7:45 a.m.) until they went to bed. Time in light and MVPA intensities were calculated using two separate intensity classifications for the LC (LC_4 and LC_5) and four classifications for the AG (AG_Treuth, AG_Puyau, AG_Trost, and AG_Freedson). Both accelerometers provided steps as outputs. DW steps were self-recorded. Repeated-measures ANOVA was used to assess overlapping monitor outputs. Results: There was no difference between DW and LC steps (Δ = 200 steps), but a nonsignificant trend was observed in the pairwise comparison between DW and AG steps (Δ = 1001 steps, P = 0.058). AG detected significantly greater steps than the LC (Δ = 801 steps, P = 0.001). Estimates of light-intensity activity minutes ranged from a low of 75.6 ± 18.4 min (LC_4) to a high of 309 ± 69.2 min (AG_Treuth). Estimates of MVPA minutes ranged from a low of 25.9 ± 9.4 min (LC_5) to a high of 112.2 ± 34.5 min (AG_Freedson). No significant differences in MVPA were seen between LC_5 and AG_Treuth (Δ = 4.9 min) or AG_Puyau (Δ = 1.7 min). Conclusion: The LC detected a comparable number of steps as the DW but significantly fewer steps than the AG in children. Current results indicate that the LC_5 and either AG_Treuth or AG_Puyau intensity derivations provide similar mean estimates of time in MVPA during-free living activity in 10-yr-old children.

A brief history of haemotopoietic stem cell Ex vivo expansion

Haematopoiesis is the process by which a hierarchy of mature and progenitor blood cells are formed. These cell populations are all derived from multipotent haematopoietic stem cells (HSC), which reside in the bone marrow ‘niche’ of adult humans. Over the lifetime of a healthy individual, this HSC population replenishes between 1010-1011 blood cells on a daily basis. Dysregulation of this system can lead to a number of haematopoietic diseases, including aplastic anaemias and leukaemias, which result in, or require for disease resolution, bone marrow cell depletion. In 1956, E. Donnall Thomas demonstrated that haematopoiesis could be restored by transplanting bone marrow-derived cells from one man into his identical twin brother, who was suffering from advanced leukaemia. His success drew significant interest in academic research and medicine communities, and 12 years later, the first successful allogeneic transplant was performed. To this day, HSCs remain the most studied and characterised stem cell population. In fact, HSCs are the only stem cell population routinely utilised in the clinic. As such, HSCs function as a model system both for the biological investigation of stem cells, as well as for their clinical application. Herein, we briefly review HSC transplantation, strategies for the ex vivo cultivation of HSCs, recent clinical outcomes, and their impact on the future direction of HSC transplantation therapy.

An analytical method for assessing stage-specific drug activity in Plasmodium vivax malaria : implications for ex vivo drug susceptibility testing

The emergence of highly chloroquine (CQ) resistant P. vivax in Southeast Asia has created an urgent need for an improved understanding of the mechanisms of drug resistance in these parasites, the development of robust tools for defining the spread of resistance, and the discovery of new antimalarial agents. The ex vivo Schizont Maturation Test (SMT), originally developed for the study of P. falciparum, has been modified for P. vivax. We retrospectively analysed the results from 760 parasite isolates assessed by the modified SMT to investigate the relationship between parasite growth dynamics and parasite susceptibility to antimalarial drugs. Previous observations of the stage-specific activity of CQ against P. vivax were confirmed, and shown to have profound consequences for interpretation of the assay. Using a nonlinear model we show increased duration of the assay and a higher proportion of ring stages in the initial blood sample were associated with decreased effective concentration (EC50) values of CQ, and identify a threshold where these associations no longer hold. Thus, starting composition of parasites in the SMT and duration of the assay can have a profound effect on the calculated EC50 for CQ. Our findings indicate that EC50 values from assays with a duration less than 34 hours do not truly reflect the sensitivity of the parasite to CQ, nor an assay where the proportion of ring stage parasites at the start of the assay does not exceed 66%. Application of this threshold modelling approach suggests that similar issues may occur for susceptibility testing of amodiaquine and mefloquine. The statistical methodology which has been developed also provides a novel means of detecting stage-specific drug activity for new antimalarials.

Disclosure obligations on ex parte application for freezing order - duty of practitioners to the court - failure to comply with duty - serious dereliction of duty to court - supplemental order for costs against solicitors personally

The decision of Applegarth J in Heartwood Architectural & Joinery Pty Ltd v Redchip Lawyers [2009] QSC 195 (27 July 2009) involved a costs order against solicitors personally. This decision is but one of several recent decisions in which the court has been persuaded that the circumstances justified costs orders against legal practitioners on the indemnity basis. These decisions serve as a reminder to practitioners of their disclosure obligations when seeking any interlocutory relief in an ex parte application. These obligations are now clearly set out in r 14.4 of the Legal Profession (Solicitors) Rule 2007 and r 25 of 2007 Barristers Rule. Inexperience or ignorance will not excuse breaches of the duties owed to the court.

#Pontiff-Ex : the Twitter community’s reaction to the Papal resignation

In this paper, we provide an account-centric analysis of the tweeting activity of, and public response to, Pope Benedict XVI via the @pontifex Twitter account(s). We focus our investigation on the particular phase around Pope Benedict XVI’s resignation to generate insights into the use of Twitter in response to a celebrity crisis event. Through a combined qualitative and quantitative methodological approach we generate an overview of the follower-base and tweeting activity of the @pontifex account. We identify a very one-directional communication pattern (many @mentions by followers yet zero @replies from the papal account itself), which prompts us to enquire further into what the public resonance of the @pontifex account is. We also examine reactions to the resurrection of the papal Twitter account by Pope Benedict XVI’s successor. In this way, we provide a comprehensive analysis of the public response to the immediate events around the crisis event of Pope Benedict XVI’s resignation and its aftermath via the network of users involved in the @pontifex account.

Myogel supports the ex-vivo amplification of corneal epithelial cells

Limbal stem cell deficiency leads to conjunctivalisation of the cornea and subsequent loss of vision. The recent development of transplantation of ex-vivo amplified corneal epithelium, derived from limbal stem cells, has shown promise in treating this challenging condition. The purpose of this research was to compare a variety of cell sheet carriers for their suitability in creating a confluent corneal epithelium from amplified limbal stem cells. Cadaveric donor limbal cells were cultured using an explant technique, free of 3T3 feeder cells, on a variety of cell sheet carriers, including denuded amniotic membrane, Matrigel, Myogel and stromal extract. Comparisons in rate of growth and degree of differentiation were made, using immunocytochemistry (CK3, CK19 and ABCG2). The most rapid growth was observed on Myogel and denuded amniotic membrane, these two cell carriers also provided the most reliable substrata for achieving confluence. The putative limbal stem cell marker, ABCG2, stained positively on cells grown over Myogel and Matrigel but not for those propagated on denuded amniotic membrane. In the clinical setting amniotic membrane has been demonstrated to provide a suitable carrier for limbal stem cells and the resultant epithelium has been shown to be successful in treating limbal stem cell deficiency. Myogel may provide an alternative cell carrier with a further reduction in risk as it is has the potential to be derived from an autologous muscle biopsy in the clinical setting.

Carcinoma ex pleomorphic adenoma : a comprehensive review of clinical, pathological and molecular data

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a carcinoma arising from a primary or recurrent benign pleomorphic adenoma. It often poses a diagnostic challenge to clinicians and pathologists. This study intends to review the literature and highlight the current clinical and molecular perspectives about this entity. The most common clinical presentation of CA ex PA is of a firm mass in the parotid gland. The proportion of adenoma and carcinoma components determines the macroscopic features of this neoplasm. The entity is difficult to diagnose pre-operatively. Pathologic assessment is the gold standard for making the diagnosis. Treatment for Ca ex PA often involves an ablative surgical procedure which may be followed by radiotherapy. Overall, patients with Ca ex PA have a poor prognosis. Accurate diagnosis and aggressive surgical management of patients presenting with Ca ex PA can increase their survival rates. Molecular studies have revealed that the development of Ca ex PA follows a multi-step model of carcinogenesis, with the progressive loss of heterozygosity at chromosomal arms 8q, then 12q and finally 17p. There are specific candidate genes in these regions that are associated with particular stages in the progression of Ca ex PA. In addition, many genes which regulate tumour suppression, cell cycle control, growth factors and cell-cell adhesion play a role in the development and progression of Ca ex PA. It is hopeful that these molecular data can give clues for the diagnosis and management of the disease.