M.Cur. (Nursing Management) / Transformational leadership involves the creation of a motivating climate that enhances growth, development, commitment, goal achievement and enjoyment which encourages behaviour based on a set of shared values (Price, 2006:124). In this study transformational leadership referred to concepts of motivation, and change management with regard to the implementation of the Cervical Cancer Screening Programme in a PRe setting. During support visits in Ekurhuleni Health District, the researcher observed a lack of transformational leadership among facility managers in Primary Health Care Clinics to transform the Cervical Cancer Screening Program in line with relevant health care legislation. It was apparent that the problems in implementing the Cervical Cancer Screening Programme were related to poor motivation and lack of implementation of change management principles in the PHC clinics. From the problem statement the following research questions emerged: To what extent is the facility manager perceived as a transformational leader to implement the Cervical Cancer Screening Programme in a PHC clinic? Which actions should the facility manager take to implement the Cervical Cancer Screening Programme in PHe? From the findings guidelines for the facility managers were described to enable them to implement a Cervical Cancer Screening Programme in a Primary Health Care clinic within legal requirements...

<p>Varje år diagnostiseras över 50 000 individer med cancer i Sverige. Ett cancerbesked väcker blandade känslor och associeras ofta med lidande och död. Ett svårt besked kan leda till en förändrad livssituation och kan även ses som början på en lång och mödosam resa. En vetenskaplig litteraturstudie baserad på 15 originalartiklar genomfördes med syftet att belysa patientens upplevelse av ett cancerbesked och därmed öka sjuksköterskans förståelse för patientens situation samt fördjupa kunskaperna inom ämnet. Genom litteraturgranskningen identifierades tre teman: information, emotionella reaktioner samt psykosocialt stöd. Patienten upplever att det är viktigt att informationen ges på ett öppet och ärligt sätt. Vidare framkom det betydelsefullt att uppmärksamma patientens emotionella reaktioner i samband med beskedet. Eftersom upplevelsen av ett cancerbesked påverkar patientens fortsatta upplevelse av sin sjukdom, har sjuksköterskan en viktig roll att fylla genom att erbjuda psykosocialt stöd i de olika tänkbara situationer som kan uppkomma i samband med ett livsavgörande besked. Fortsatt forskning behövs för att jämföra hur de rekommendationer som finns angående delgivandet av ett svårt besked överensstämmer med patienternas egna upplevelser och önskemål.</p> / <p>Every year, over 50 000 individuals in Sweden are diagnosed with cancer. The disclosure of the cancer diagnosis arouses emotions and is often associated with suffering and death. Receiving bad news may lead to changes in life and can also be seen as the beginning of a long and difficult journey. A scientific study based on 15 original articles was carried out with the purpose to identify the patient’s experience of receiving a cancer diagnosis and therefore increase the nurse’s understanding for the patient’s situation and deepen the knowledge of the subject. When examining the articles three themes were identified: information, emotional reactions and psychosocial support. The patient experience that it is important that the information is given in an open and honest manner. Patients also find it important that their emotional reaction is being observed as receiving the diagnosis. As the disclosure of the cancer diagnosis affects the patient’s further perception of the disease the nurse has an important role providing psychosocial support in various situations that may arise in connection with the disclosure. Continued research is needed to compare how guidelines for giving bad news to a patient correspond with the patient’s own experiences and preferences.</p>

Darmkrebs ist die zweithäufigste malignombedingte Todesursache in den westlichen Industrieländern. Durch eine frühzeitige Diagnose besteht jedoch eine hohe Chance auf Heilung. Der Goldstandard zur Darmkrebsfrüherkennung ist gegenwärtig die Koloskopie. Eine Darmspiegelung ist jedoch invasiv und mit Unannehmlichkeiten für den Patienten verbunden. Die Akzeptanz in der Bevölkerung ist daher gering. Ziel des BMBF- Projektes „Entwicklung eines nichtinvasiven Nachweissystems zur Früherkennung von humanem Darmkrebs“, in dessen Rahmen diese Arbeit entstand, ist die Bereitstellung eines nichtinvasiven Nachweisverfahrens zur Darmkrebsfrüherkennung. Der Nachweis soll über die Detektion von aus neoplastischen Zellen stammender DNA in Stuhl erfolgen. Die Entartung dieser Zellen beruht auf Veränderungen im Erbgut, welches unter anderem Mutationen sind. Im ersten Teil des BMBF-Projektes wurde ein Set von Mutationen zusammengestellt, welches eine hohe Sensitivität für Vorstufen von Darmkrebs aufweist. Ziel dieser Arbeit war es, eine Nachweismethode für die zuvor identifizierten Punktmutationen zu entwickeln. Das Nachweisverfahren musste dabei unempfindlich gegen einen hohen Hintergrund nichtmutierter DNA sein, da im Stuhl geringe Mengen DNA aus neoplastischen Zellen bei einem hohen Hintergrund von DNA aus gesunden Zellen vorliegen. Hierzu wurden Plasmidmodellsysteme für die aus dem Marker-Set stammenden Genfragmente BRAF und dessen Mutante V600E, CTNNB1 und T41I, T41A, S45P und K-ras G12C hergestellt. Mit Hilfe dieser Plasmidmodellsysteme wurde dann das Nachweissystem entwickelt. Der entscheidende Schritt für die Detektion von Punktmutationen bei hohem Wildtypüberschuss ist eine vorhergehende Anreicherung. In der vorliegenden Arbeit wurde dazu die Methode der LNA-clamp-PCR (locked nucleic acid) etabliert. Die Bewertung der erzielten Anreicherung erfolgte über das relative Detektionslimit. Zur Bestimmung des Detektionslimits wurde die Schmelzkurvenanalyse von Hybridisierungssonden eingesetzt; diese wurde im Rahmen dieser Arbeit für die drei oben genannten Genfragmente und ihre Mutanten entwickelt. Die LNA-clamp-PCR wird in Anwesenheit eines LNA-Blockers durchgeführt. Das Nukleotidanalogon LNA weist im Vergleich zu DNA eine erhöhte Affinität zu komplementären DNA-Strängen auf. Gleichzeitig kommt es bei Anwesenheit einer Basenfehlpaarung zu einer größeren Destabilisierung der Bindung. Als Blocker werden kurze LNA-DNA-Hybridoligonukleotide eingesetzt, die den mutierten Sequenzbereich überspannen und selbst der Wildtypsequenz entsprechen. Durch Bindung an die Wildtypsequenz wird deren Amplifikation während der PCR verhindert (clamp = arretieren, festklemmen). Der Blocker selbst wird dabei nicht verlängert. Der Blocker bindet unter optimalen Bedingungen jedoch nicht an die mutierte Sequenz. Die Mutante wird daher ungehindert amplifiziert und somit gegenüber dem Wildtyp-Fragment angereichert. Die Position des Blockers kann im Bindungsbereich eines der Primer sein und hier dessen Hybridisierung an dem Wildtyp-Fragment verhindern oder zwischen den beiden Primern liegen und so die Synthese durch die Polymerase inhibieren. Die Anwendbarkeit beider Systeme wurde in dieser Arbeit gezeigt. Die LNA-clamp-PCR mit Primerblocker wurde für BRAF etabliert. Es wurde ein Detektionslimit von mindestens 1:100 erzielt. Die LNA-clamp-PCR mit Amplifikationsblocker wurde erfolgreich für BRAF, K-ras und CTNNB1: T41I, T41A mit einem Detektionslimit von 1:1000 bis 1:10 000 entwickelt. In Stuhlproben liegt DNA aus neoplastischen Zellen nach Literaturangaben zu einem Anteil von 1% bis 0,1% vor. Die LNA-clamp-PCR weist also mit Amplifikationsblockern ein ausreichend hohes Detektionslimit für die Analyse von Stuhlproben auf. Durch die erfolgreiche Etablierung der Methode auf drei verschiedenen Genfragmenten und vier unterschiedlichen Punktmutationen konnte deren universelle Einsetzbarkeit gezeigt werden. Für die Ausweitung der LNA-clamp-PCR auf die übrigen Mutationen des Marker-Sets wurden Richtlinien ausgearbeitet und die Blockereffizienz als Kennzahl eingeführt. Die LNA-clamp-PCR ist ein schnelles, kostengünstiges Verfahren, welches einen geringen Arbeitsaufwand erfordert und wenig fehleranfällig ist. Sie ist somit ein geeignetes Anreicherungsverfahren für Punktmutationen in einem diagnostischen System zur Darmkrebsfrüherkennung. Darüber hinaus kann die LNA-clamp-PCR auch in anderen Bereichen, in denen die Detektion von Punktmutationen in einem hohen Wildtyphintergrund erforderlich ist, eingesetzt werden. / Colon cancer is the second leading cause of cancer related deaths in the western world. However if diagnosed early there is a great chance curing the disease. Coloscopy is the gold standard for early detection of colorectal cancer today. Its greatest disadvantage is the fact that it is an invasive technique and provides some discomfort for the patients. Therefore, the compliance to undergo such a procedure is extremely low. This work was generated in the context of the BMBF-project „Development of a non-invasive assay for the early detection of preneoplastic and neoplastic lesions in the human colon“. The aim of the work described here is the development of a non-invasive assay for the early detection of colon cancer. The assay should detect DNA from neoplastic cells in feces samples. The transformation of these cells is based on alterations in the genome predominantly mutations. In the first part of the BMBF-project a mutation panel with high sensitivity for preneoplastic lesions of colon cancer was determined. The aim of this work was to develop a detection method for the point mutations of the determined mutation panel. The rare mutant DNA needs to be detected in the presence of a great amount of wild-type DNA shed from healthy tissue. The assay system needs to be insensitive to this high background of healthy DNA. Therefore a model system of plasmid DNA containing gene fragments of BRAF and its mutation V600E, CTNNB1 and T41I, T41A, S45P and K-ras G12C obtained from the marker panel was established. Using these plasmid system the detection method was developed. The most critical parameter for the detection of rare point mutations is an enrichment of these rare DNA molecules. In this work LNA-clamp-PCR (locked nucleic acid) technology was used to enrich the mutant DNA.. For the estimation of the achieved enrichment the relative detection limit was used. The detection limit was determined by melting curve analysis of hybridization probes. These assays were established in the present work for the three above mentioned gene fragments. LNA-clamp-PCR is performed in the presence of an LNA blocker. LNA is a synthetic DNA analog. LNA nucleotide analog bind to complementary DNA strands with higher affinity. In addition a single mismatch in the LNA-DNA duplex causes a much greater destabilization compared to a DNA-DNA duplex. Short LNA-DNA-hybrids were used as clamp, which cover the mutated region and represent the wild-type sequence. Within an appropriate temperature range, LNA can specifically bind to wild type template and can inhibit its amplification. The clamp itself will not be elongated. Under optimal conditions the LNA clamp will not interfere with the amplification of the mismatched template. Therefore the mutated gene fragment will be enriched in comparison to the wild-type. The position of the LNA clamp can either be at the primer binding site inhibiting primer hybridization on the wild-type fragment or the LNA clamp is positioned between the two primer binding sites inhibiting chain elongation of the perfectly matched template. In the present work both systems were applied. For the gene fragment BRAF the LNA was used at the primer binding site. The achieved detection limit was at least 1:100. The LNA-clamp-PCR with LNA inhibiting the chain elongation were developed successfully for BRAF, K-ras and CTNNB1: T41I, T41A achieving a detection limit of 1:1000 to 1:10 000. According to the literature 1% to 0.1% of the DNA in feces derives from neoplastic cells. Therefore the detection limit achieved by LNA-clamp-PCR with LNA inhibiting chain elongation would be sufficient for analyzing feces samples. LNA-clamp-PCR protocols were established for three different gene fragments and four diverse point mutations indicating that the technology can generally be used for high sensitive detection of DNA mutations. For the development of LNA-clamp-PCR protocols for the other mutations of the marker panel development guidelines were established. Clamp efficiency was identified as a quantitative parameter for protocol optimization. The LNA-clamp-PCR is a robust, fast and cost-saving technique which needs low labor input. Therefore the method is adequate for enriching point mutated gene fragments in a diagnostic assay for the detection of early colon cancer stages. In addition LNA-clamp-PCR can be applied in other fields where rare sequence variations need to be detected in the presence of high wild-type DNA background.

This thesis describes the development of a combined label-free imaging and analytical strategy for intraoperative characterization of cancer lesions using the coherent anti-Stokes Raman scattering imaging (CARS) technique. A cell morphology-based analytical platform is developed to characterize CARS images and, hence, provide diagnostic information using disease-related pathology features. This strategy is validated for three different applications, including margin detection for radical prostatectomy, differential diagnosis of lung cancer, as well as detection and differentiation of breast cancer subtypes for in situ analysis of margin status during lumpectomy. As the major contribution of this thesis, the developed analytical strategy shows high accuracy and specificity for all three diseases and thus has introduced the CARS imaging technique into the field of human cancer diagnosis, which holds substantial potential for clinical translations. In addition, I have contributed a project aimed at miniaturizing the CARS imaging device into a microendoscope setup through a fiber-delivery strategy. A four-wave-mixing (FWM) background signal, which is caused by simultaneous delivery of the two CARS-generating excitation laser beams, is initially identified. A polarization-based strategy is then introduced and tested for suppression of this FWM noise. The approach shows effective suppression of the FWM signal, both on microscopic and prototype endoscopic setups, indicating the potential of developing a novel microendoscope with a compatible size for clinical use. These positive results show promise for the development of an all-fiber-based, label-free imaging and analytical platform for minimally invasive detection and diagnosis of cancers during surgery or surgical-biopsy, thus improving surgical outcomes and reducing patients' suffering.

Cancer is a world menace. After years of endeavor seeking the end of it, people started to realize that no matter how powerful the therapy could be, detection at early stage is always a cheaper, easier and more successful solution compared with curative methods for cancer developed onto its advanced stage. However, relatively few early-detection approaches have proven sufficiently effective and practical for mass use as a point-of-care tool. An early-cancer screening tool integrating the desired features of sensitive, informative, portable, and cost-effective is in need for the doctors. The progress in optical imaging and Micro-electro-mechanical system (MEMS) technology offers a promise for an innovative cancer screening alternative that is non-invasive, radiation-free, portable and potentially cost-effective. This dissertation investigates handheld instrumentation as multi-modalities of miniature imaging probes with various designs of MEMS devices, to obtain real-time images of epithelial tissue optical and physiological properties, combining the quantitative advantages of spectral analysis with the qualitative benefits of imaging to distinguish early cancer. This dissertation in sequence presents the handheld instruments in the fashions of Laser-scanning confocal microscopy (LSCM), optical diffuse reflectance imaging, nonlinear optical imaging modalities with their subsequent image-guided managements in oral cancer, skin cancer detection, circulating tumor cell (CTC) imaging, and imaging guided surgeries. One of the main challenges facing miniaturization lies in the mechanism of beam deflection across the sample. This dissertation introduces two generations of MEMS devices desgined, fabricated and incorporated in the imaging probes. A two-axis vertical comb driven silicon micromirror was used in the development of a handheld LSCM for oral cancer detection. Though obtaining numerous advantages, this first generation silicon MEMS micromirror suffers from small aperture size and high voltage requirement for actuation, which result in low collection efficiency in fluorescence imaging and medial safety concerns, respectively. Therefore a stainless steel scanner compatible with electrical discharge machining (EDM) process was fabricated with simplified process, low-voltage magnetic actuation and large fluorescence collection efficiency, with its capability demonstrated in the incorporation and embodiment of a handheld hyperspectral nonlinear imaging probe. Besides, software and controlling innovations for handheld imaging modalities are presented. A feedback controlling system for MEMS scanning status monitoring was developed for stabilized imaging rendering. For the sake of further improved imaging stability in handheld imaging and to enable on-site mosaic for large field viewing, a handheld mosaic system was developed and presented. / text

published_or_final_version / Public Health / Master / Master of Public Health

Oral cancer is the sixth most common cancer worldwide and has been marked by high morbidity and poor survival rates that have changed little over the past few decades. Beyond prevention, early detection is the most crucial determinant for successful treatment and survival of cancer. Yet current methodologies for cancer diagnosis based upon pathological examination alone are insufficient for detecting early tumor progression and molecular transformation. Development of new diagnostic tools incorporating tumor biomarkers could enhance early detection by providing molecular-level insight into the biochemical and cellular changes associated with oral carcinogenesis. The work presented in this doctoral dissertation aims to address this clinical need through the development of new automated cellular analysis methods, incorporating lab-on-a-chip sensor techniques, for examination of molecular and morphological biomarkers associated with oral carcinogenesis. Using the epidermal growth factor receptor (EGFR) as a proof-of-principle biomarker, the sensor system demonstrated capacity to support rapid biomarker analysis in less than one-tenth the time of traditional methods and effectively characterized EGFR biomarker over-expression in oral tumor-derived cell lines. Successful extension from in vitro tumor cell lines to clinically relevant exfoliative brush cytology was demonstrated, providing a non-invasive method for sampling abnormal oral epithelium. Incorporation of exfoliative cytology further helped to define the important assay and imaging parameters necessary for dual molecular and morphological analysis in adherent epithelium. Next, this new sensor assay and method was applied in a small pilot study in order to secure an initial understanding of the diagnostic utility of such biosensor systems in clinical settings. Four cellular features were identified as useful indicators of cancerous or pre-cancerous conditions including, the nuclear area and diameter, nuclear-to-cytoplasm ratio, and EGFR biomarker expression. Further examination using linear regression and ROC curve analysis identified the morphological features as the best predictors of disease while a combination of all features may be ideal for classification of OSCC and pre-malignancy with high sensitivity and specificity. Further testing in a larger sample size is necessary to validate this regression model and the LOC sensor technique, but shows strong promise as a new diagnostic tool for early detection of oral cancer. / text

Optical assays to detect cancer-associated molecular biomarkers in biological substrates are commonly performed with antibody-targeted organic dye contrast agents but the potential for precise quantification, long-term imaging, and multiplexed readouts is limited by chemical and optical instability, non-optimal spectral characteristics, and complicated synthetic chemistry of the dyes. This dissertation tested the hypothesis that a novel class of optical contrast agents termed polymer-protected Raman-encoded nanoparticle tags (PRENTs) provides practical advantages over existing optical technologies for molecular diagnostic applications. First, PRENTs were developed through a modular design utilizing gold-nanoparticle-Raman reporter complexes protected and functionalized by polyethylene glycol derivatives. PRENTs produced optical readouts through surface enhanced Raman scattering (SERS) that were brighter and more photostable than the fluorescence of semiconductor quantum dots under identical experimental conditions. Unique spectral signatures were produced with a broader class of Raman reporters than is possible with silica coated Raman tags. Spectral signatures and colloidal stability of PRENTs were unaffected by harsh chemical conditions that cause spectral changes and aggregation of dyes, quantum dots, and protein coated Raman tags. Antibody-targeted PRENTs specifically tagged cell surface cancer biomarkers on living cells at reasonable integration times. PRENTs were non-toxic to cells under conditions exceeding those required for sensitive molecular detection. Next, PRENTs were efficiently optimized for excitation with near-infrared light through inclusion of near-infrared chromophores as Raman reporters and exploitation of the size-dependent optical enhancement of gold nanoparticles. Third, the development of a slide-based Raman-linked immunosorbent assay using antibody-conjugated PRENTs enabled quantification of protein biomarkers with a dynamic range of 3 to 4 logs. In summary, this dissertation establishes PRENTs as novel optical tags with unique features useful for biomedical applications and provides insights for further assay development.

[Truncated abstract] Ovarian cancer is currently the leading cause of death from gynaecological malignancies in women from developed countries. Serous ovarian cancer is the most prevalent type of all ovarian cancers, with the majority diagnosed in an advanced stage where treatment efficacy is reduced and patient survival is poor. Because of this fact, the development of improved detection and treatment strategies are necessary, with much research focussing on the complex molecular pathways involved in ovarian tumour growth as one potential avenue for intervention. Apoptosis, or programmed cell death, is one such area of investigation because currently successful cancer treatments induce apoptosis in tumour cells. Molecular analysis of apoptosis in both normal tissue and tumours has established a positive relationship between increased expression of secreted frizzled-related protein 4 (SFRP4) and apoptosis, however to date, very little research has focussed on the role of this gene in the ovary . . . An examination of SFRP4 and β-catenin expression in 163 primary serous ovarian carcinomas revealed high SFRP4 expression was associated with low β-catenin expression and conversely, low SFRP4 was associated with high β-catenin expression in the majority of the ovarian tumours analysed, reinforcing the inverse relationship observed in the ovarian cell lines. A positive trend was observed between cancer stage and the expression level of these proteins, with increased SFRP4 expression and reduced β-catenin expression as cancer stage increased. Additionally, patient survival revealed a trend towards increased survival among ovarian cancer patients who had tumours expressing low levels of SFRP4. Taken together, the novel findings of this study indicate that the increased expression of SFRP4 observed in a large proportion of serous ovarian cancers is a cellular response to down-regulate the level of β-catenin, and thus an attempt to maintain cellular homeostasis by counteracting the excessive proliferating signals present in these tumour cells.

Inledning: Med tiden har folkhälsa och vad som ses som folksjukdomar förändrats. Idag har vi folksjukdomar som inte var vanliga för årtionden sedan, sjukdomar som nu blivit ett globalt folkhälsoproblem. En av dessa sjukdomar är cancer. Bröstcancer är den vanligaste cancerform för kvinnor. Brösten är en stor del för att en kvinna ska känna sig kvinnlig. Syfte: Syftet med denna litteraturstudie är att beskriva kvinnans psykiska hälsa efter en bröstcancerdiagnos med fokus på ångest, depression och stress. Metod: Vald metod är en systematisk litteraturöversikt. Artiklar söktes i databasen PubMed som analyserades systematiskt. Under sökprocessen valdes 15 vetenskapliga artiklar ut med relevant information för att svara på syftet till studien. Tre teman valdes ut under analysen av artiklarna. Temaorden: Rädsla för återfall av bröstcancer, kvinnlighet, psykologiska hälsoeffekter. Resultat: Resultatet visar att kvinnor känner sig mindre kvinnlig och attraktiv när ett bröst opererats bort. Kvinnor med en bröstcancerhistorik är rädd för att få ett återfall vilket påverkar deras liv genom oro, ångest och stress. Yngre kvinnor är mer rädd för döden än äldre vilket kan bero på, yngre kvinnor har små barn och är rädd för att inte se barnen växa upp. Diskussion: En bröstcancerdiagnos kan vända upp och ner på tillvaron för en kvinna. Efter att hon har fått en diagnos behöver hon ändra om sin planering inför framtiden Detta kan skapa ångest och oro inför hur det kommer att bli, hur hon kommer att må samt oro för vilken utgång sjukdomen har. Det finns ett behov för mer träning för läkaren och sjuksköterskor för att bättre hjälpa bröstcancerpatienter med psykologiska konsekvenser. / Introduction: Over time, disease patterns affecting the population have changes. Today, many people are diagnosed with diseases that were not common decades ago, which have now become a global public health problem. One of these diseases is cancer. Breast cancer is the most common cancer form for women, and stressful in part because of the association of breasts with femininity.   Purpose: The purpose of this literature study is to describe the mental health of the woman after a breast cancer diagnosis focusing on anxiety, depression and stress. Method: The chosen method is a systematic literature review. Articles have been systematically searched in the PubMed database. During the search process, 15 scientific articles were selected with relevant information to respond to the purpose of the study. Three themes emerged during the analysis of the articles: Fear of breast cancer recurrence, femininity, and psychological health effects. Result: The results show that women feel less feminine and attractive when a breast has been removed. Women with breast cancer history are afraid of recurrence which affects their lives through anxiety, anxiety and stress. Younger women are more afraid of death than older women, which may be because younger women have young children and are fearful of not seeing them grow up. Discussion: A breast cancer diagnosis can strongly affect a woman. After a woman's diagnosis, she needs to change her planning for the future. This can create anxiety and anxiety about recovery and how she will feel and lead to worry about the outcome of the disease. There is a need for more training for doctors and nurses to better help breast cancer patients who experience stress, anxiety and depression.