Introduktion Lungcancer är den tredje vanligaste cancersjukdomen i Sverige och den främsta orsaken till cancerrelaterade dödsfall i världen. Den har en dålig prognos med en 5 års överlevnad på under 25%. Detta främst på grund av att den ofta upptäcks i ett sent skede då bot inte längre är möjligt. Den vanligaste orsaken till lungcancer är rökning. Ungefär 90% av alla som drabbats av lungcancer är eller har varit rökare. Med hjälp av screening av individer med en hög konsumtion av rökning “högriskindivider” kan lungcancer hittas i ett tidigt skede och förhindra att individer dör av sjukdomen. Syfte Syftet med detta examensarbete är belysa högriskindividers upplevelser av deltagande i lungcancerscreening samt deras eventuella behov av stöd från sjukvården för att öka motivationen till att delta i lungcancerscreening. Metod En allmän litteraturstudie baserat på 18 vetenskapliga artiklar med kvalitativ ansats varav 3 med mixad-metod Resultat Resultatet baseras på 18 vetenskapliga artiklar. Fyra kategorier och tio subkategorier blev syntesen av dessa studier. De fyra kategorier som presenteras är: 1. Fördelar med screening, 2. Nackdelar med screening, 3. Delaktighet i beslutsprocessen och förtroendet för vården samt 4. Personcentrerad individanpassad information. Resultatet visar på vikten av personcentrerad och individanpassad information samt betydelsen av förtroendet för vården inför och under screeningprocessen. Slutsats Fördelarna med att screenas för lungcancer övervägde nackdelarna. Det kunde även motivera individer att sluta röka och behålla kontrollen över sin hälsosituation och minska rädslan för det okända. Nackdelarna var att individer kunde uppleva psykisk oro och stress under screeningprocessen och en rädsla för en cancerdiagnos. Bemötandet från vårdpersonalen var 3av stor betydelse och behovet av individanpassad information var stort. Pilotstudier pågår i Sverige för en eventuell implementering av lungcancerscreening i Sverige i framtiden. / BackgroundLung cancer is the leading cause of cancer-related deaths worldwide and the third most common in Sweden. It has a poor prognosis with a 5-year survival rate of below 25%. This is mainly due to the fact that it is often discovered at a late stage where cure is no longer possible. The most common cause of lungcancer is smoking. Approximately 90% of all people affected by lungcancer are or have been smokers. With the help of screening "highrisk individuals" lung cancer can be found at an early stage and thus prevent individuals from dying of the disease. Research questionThe purpose of this thesis is to illustrate high-risk individuals' experiences of participation in lung cancer screening and their possible need for support from health care to increase the motivation to participate in lung cancer screening. MethodA general literature review based on 18 scientific articles with a qualitative approach, of which 3 with mixed-method ResultsThe result is based on 18 scientific articles. Four categories and ten subcategories became the synthesis of these studies. The four categories presented are: 1. Advantages of screening, 2. Disadvantages of screening, 3. Participation in the decision-making process and trust in health care, and 4. Person-centered personalized information. The results show the importance of person-centered and individualized information as well as the importance of trust from the healthcare system before and during the screening process. ConclusionThe advantages of being screened for lung cancer outweighed the disadvantages. It could also motivate individuals to quit smoking and maintain control over their health situation and reduce fear of the unknown. The disadvantages were that individuals could experience 4psychological anxiety and stress during the screening process and a fear of a cancer diagnosis. How the individual was treated by the care staff was of great importance and the need for individually tailored information was great.Pilotstudies are ongoing in Sweden for a possible implementation of lung cancer screening in Sweden in the future.

Despite the existence of breast cancer screening that could promote early diagnosis and survival of breast cancer, high mortality rates of breast cancer persist among Filipino women. The purpose of the qualitative study was to describe the perceptions, beliefs, and behaviors of Filipino women working as Overseas Filipino Workers (OFWs) in Saudi Arabia. Face-to-face interviews were conducted with 20 Filipino women between the ages of 40 to 60 years who were recruited voluntarily using purposeful sampling technique. Guided by the structures of health belief model (HBM), the study used an inductive coding technique to elicit common themes from the raw data. The study established that the participants' screening behaviors were influenced by family history of breast cancer, the financial and emotional burden of the disease and its treatment, the benefit of early detection, mobility to participate, culture and language barriers, and the social media. The study also demonstrated that the desire to participate in breast cancer screening is influenced by the participants' perception of susceptibility and perception of severity to breast cancer. The findings of the study could create a positive social change as it may inform the practice of public health providers, influence the drafting of informed policies for comprehensive breast health care, and improve access to preventive health services for Filipino women OFWs. Furthermore, the study could empower Filipino women in their personal health decision making, especially when working in other countries where good health is the working capital and a precondition for survival.

Bakgrund: Våld i nära relation ses som ett globalt folkhälsoproblem där kvinnor världen över faller offer för våldet. Det som kännetecknar våld i nära relation är att det finns en relation och känslomässigt band mellan offer och förövare. Våldet kan ge uttryck fysiskt, psykiskt, sexuellt, materiellt, ekonomiskt och socialt. Tidigare forskning visade att cirka var tredje kvinna som varit i en relation har utsatts för någon form av våld. Enligt Världshälso-organisationen (WHO) bör hälso- och sjukvården vara drivande i arbetet mot våld i nära relationer. Syfte: Syftet med studien var att undersöka hur yrkesverksamma inom hälso- och sjukvården kan identifiera tecken på att kvinnor blivit utsatta för våld i nära relation. Metod: Litteraturöversikt användes som metod till studien. Åtta kvalitativa och en kvantitativ artikel valdes ut. Resultat: Hälso- och sjukvårdspersonal var ofta de första som mötte kvinnor som utsatts för våld i nära relation. Sjukvården arbetar utifrån olika screeningmetoder där bland annat frågor ställs för att utforska kvinnans situation och hälsa. Det var viktigt att screening genomfördes för att identifiera om eventuell våldsproblematik fanns. Utifrån artiklarnas resultat framträdde tre subteman och ett huvudtema som svarade till studiens syfte. Konklusion: Studiens resultat visade att hälso- och sjukvården var medvetna om kvinnans utsatthet för våld i nära relation. Sjukvården hade ett flertal metoder som rekommenderades att arbeta efter, dock fanns det hinder som resulterade i att screening inte användes på rätt sätt och i vissa fall inte användes alls. Det finns förbättringsområden i sjukvårdens arbete med våldsutsatta kvinnor. / Background: Intimate partner violence is a global public health problem where women all around the world fall victims to violence. Intimate partner violence is the relationship and emotional bond between victim and perpetrator. Violence can manifest in several different ways, such as physical, mental, sexual, material, economic or social. Previous research showed that about every third woman who had been in a relationship were victims to some form of violence. According to the World Health Organization (WHO) health care services should be a driving force in the work against intimate partner violence.  Aim: The aim of the study was to investigate how health care professionals can identify expose of intimate partner violence among women.  Method: A literature review was conducted. Eight qualitative and one quantitative article were selected.  Results: Health care professionals are often the first to meet the woman who has been subjected to violence. The health care services used various screening methods where, questions are asked to explore the woman's situation. Based on the results of the articles, a main theme and three sub-themes were constructed.  Conclusion: The result of this study shows that the health care services are aware of the woman's exposure to violence. The health care system has several methods that they should work with, however there are many obstacles that result in both screening not being used correctly and in some not being used at all. There are areas for improvement in health care work with women exposed to violence.

Obwohl fetale Mißbildungen seit langem bekannt sind, wird eine intensive Prüfung von Arzneimitteln und anderen Substanzen erst seit den 1960er Jahren durchgeführt. Dem Tierschutzbericht von 2001 ist zu entnehmen, daß im Jahr 1999 insgesamt etwa 1,6 Millionen Wirbeltiere zu Versuchszwecken benötigt wurden. Als mögliche Alternative zu Untersuchungen mit Säugetieren wurde ein Testmodell mit Embryonen des Zebrabärblings (D. rerio) entwickelt. Ziel der vorliegenden Arbeit ist es zu klären, ob sich mit den Embryonen von Danio rerio ein teratogenes Potential von Substanzen erkennen und quantifizieren läßt. Dazu wurde DarT (?Danio rerio Teratogenicity Assay?) als Teratogenitäts-Screening Test entwickelt. Es können anhand von toxikologischen Endpunkten sowohl die letalen als auch die subletalen Wirkungen von Substanzen bestimmt werden. Darüber hinaus werden anhand von teratogenen Endpunkten speziell Malformationen erfaßt. Der Vergleich der beobachteten Effekte und der daraus berechneten Wirkkonzentrationen gestattet eine Einschätzung des teratogenen Potentials von Substanzen. Die im DarT erzielten Ergebnisse werden mit der bekannten Zuordnungen des ?säugerteratogenen? Potentials verglichen. Für 88 % der getesteten Substanzen gibt DarT die aus säugertoxikologischen Untersuchungen bekannten Einordnungen hinsichtlich des teratogenen Potentials wieder. Für 10 % der Testsubstanzen wurde das teratogene Potential zu hoch, für 2 % zu niedrig eingeschätzt. Mit dem Testsystem ?Danio rerio Teratogenicity Assay ? DarT? ist ein Vergleich von Substanzen hinsichtlich ihres teratogenen und allgemein toxischen Potentials möglich. In einem Modell können Wirkkonzentrationen und Konzentrations-Wirkungs-Beziehung ermittelt und direkt verglichen werden. Mit DarT kann eine große Anzahl von Substanzen zeit- und kostengünstig untersucht werden. Die aus Untersuchungen mit Säugetieren bekannten Zuordnungen der teratogenen Potentiale von Substanzen wird gut wiedergegeben.

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Gegenwärtig ist das Interesse und der Bedarf von Proteinbindern insbesondere in der Biotechnik und Pharmaforschung sehr groß. Kombinatorische, Partikel-basierte (One-Bead-One-Compound) Peptidbibliotheken sind eine Technik, um selektiv bindende Proteine zu identifizieren. Allerdings beinhaltet das Screening dieser Peptidbibliotheken aufwendige Schritte, wie die Separation, Sequenzierung und Charakterisierung von identifizierten Bindern. In dieser Arbeit wurde ein Chip-System entwickelt, auf dem alle Schritte eines Screenings durchgeführt werden können. Dafür wurde ein Glasobjektträger mit einem magnetisch leitenden, doppelseitigen Klebeband versehen. Die Partikel der Bibliothek wurden durch ein Sieb aufgetragen. Dies führte zu einer geordneten Immobilisierung der Partikel auf dem Chip. Über 30.000 Partikel konnten so auf einem Chip immobilisiert werden. Für die Identifizierung von selektiven Protein-bindenden Peptiden wird die immobilisierte Peptidbibliothek mit einem Fluorophor-markierten Protein inkubiert, bindende Partikel mittels Fluoreszenzscan identifiziert und die Peptidsequenz direkt auf dem Chip mittels Matrix-Assisted-Laser-Desorption/Ionization-(MALDI)-Flugzeit-(TOF)-Massenspektroskopie (MS) bestimmt. Die Durchführung einer Abbruchsequenz-Methode erlaubt die eindeutige Bestimmung der Peptidsequenzen mit einer nahezu 100 % Genauigkeit. Die entwickelte Technologie wurde in einem FLAG-Peptid-Modell validiert. Bei dem Screening wurden neue anti-FLAG-Antikörper-bindende Peptide identifiziert. Anschließend wurden in einem Screening von ca. 30.000 Partikeln IgG-bindende Peptide mit mittleren mikromolaren Dissoziationskonstanten identifiziert. Für die Identifizierung stärkerer Binder wurde eine magnetische Anreicherung entwickelt, die dem Chip-Screening vorgeschaltet werden kann. Hiermit wurden aus ca. 1 Million gescreenter Partikel, Peptide mit Dissoziationskonstanten im niedrigen mikromolaren Bereich identifiziert. / The screening of one-bead-one-compound (OBOC) libraries is a well-established technique for the identification of protein-binding ligands. The demand for binders with high affinity and specificity towards various targets has surged in the biomedical and pharmaceutical field in recent years. The combinatoric peptide screening traditionally involves tedious steps such as affinity selection, bead picking, sequencing and characterization. In this thesis, a high-throughput “all-on-one chip” system is presented to avoid slow and technically complex bead picking steps. Beads of a combinatorial peptide library are immobilized on a conventional glass slide equipped with an electrically conductive tape. The beads are applied by using a precision sieve, which allows the spatially ordered immobilization of more than 30,000 beads on one slide. For the target screening, the immobilized library is subsequently incubated with a fluorophore-labeled target protein. In a fluorescence scan followed by matrix-assisted laser desorption/ionization (MALDI)-time of flight (TOF) mass spectrometry (MS), high-affinity binders are directly and unambiguously sequenced directly from the bead. The use of an optimized ladder sequencing approach improved the accuracy of the de-novo sequencing step to 100 %. This new technique was validated by employing a FLAG-based model system. In a first step, new peptide binders for the M2 anti-FLAG monoclonal antibody were identified. Finally, this system was utilized to screen for IgG-binding peptides. The screening of about 30.000 peptides on one chip led to the identification of peptide binders in the mid micromolar range. A magnetic enrichment technique was developed to increase the number of screened beads. By combining the magnetic enrichment strategy with the chip system, 1 million beads were screened and IgG-binders in the low micromolar range were identified.

Master of Science / Department of Biochemistry and Molecular Biophysics / Phillip Klebba / Iron acquisition is a component of Gram-negative bacteria pathogenesis, therefore as a form of 'nutritional immunity' host organisms sequester iron. To obtain iron bacteria secrete siderophores that scavenge iron. The E. coli outer membrane protein FepA actively transports the siderophore ferric enterobactin into the periplasm. We observe this uptake reaction by fluorescently labeling FepA in live bacteria, monitoring quenching that occurs upon binding of FeEnt, and then fluorescence recovery during transport. Energy poisons azide, arsenate, and 2,4-dinitrophenol were evaluated to determine sensitivity to known transport inhibitors. We developed and optimized methods to screen for iron transport inhibitors using a cell-based high-throughput screening platform. These inhibitors may have broad spectrum bacteriostatic antibiotic properties.

Colorectal cancer is second only to lung cancer as a leading cause of internal cancer death. Individuals over 65 years of age are most at risk yet least likely to engage in screening for colorectal cancer. The purpose of this descriptive-correlational study using a modified Pender Health Promotion Model was to identify motivations of elderly individuals to engage in health protective behavior. A convenience sample of 90 subjects answered a four-part motivations questionnaire in which three subscales--early detection, powerful others, and chance--met reliability standards (alpha >.70). Chance was significantly related to compliance (r = -.28; p =.003); Hemoccult compliers believed less in chance and powerful others than did non-compliers (p =.005;.002). The 88 percent who performed a Hemoccult stool test as a screening method for early detection of colorectal cancer demonstrated that these elders willingly engaged in health protective behavior and supported the nurses' role in promoting primary prevention in elderly clients.

Drug discovery has witnessed an increase in the application of in silico methods to complement existing in vitro and in vivo experiments, in an attempt to 'fail fast' and reduce the high attrition rates of clinical phases. Computer algorithms have been successfully employed for many tasks including biological target selection, hit identification, lead optimization, binding affinity determination, ADME and toxicity prediction, side-effect prediction, drug repurposing, and, in general, to direct experimental work. This thesis describes a multifaceted approach to virtual screening, to computationally identify small-molecule inhibitors against a biological target of interest. Conformer generation is a critical step in all virtual screening methods that make use of atomic 3D data. We therefore analysed the ability of computational tools to reproduce high quality, experimentally resolved conformations of organic small-molecules. We selected the best performing method (RDKit), and developed a protocol that generates a non-redundant conformer ensemble which tends to contain low-energy structures close to those experimentally observed. We then outline the steps we took to build a multi-million, small-molecule database (including molecule standardization and efficient exact, substructure and similarity searching capabilities), for use in our virtual screening experiments. We generated conformers and descriptors for the molecules in the database. We tagged a subset of the database as `drug-like' and clustered this to provide a reduced, diverse set of molecules for use in more computationally-intensive virtual screening protocols. We next describe a novel virtual screening method we developed, called Ligity, that makes use of known protein-ligand holo structures as queries to search the small-molecule database for putative actives. Ligity has been validated against targets from the DUD-E dataset, and has shown, on average, better performance than other 3D methods. We also show that performance improved when we fused the results from multiple input structures. This bodes well for Ligity's future use, especially when considering that protein structure databases such as the Protein Data Bank are growing exponentially every year. Lastly, we describe the fruitful application of structure-based and ligand-based virtual screening methods to Plasmodium falciparum Subtilisin-like Protease 1 (PfSUB1), an important drug target in the human stages of the life-cycle of the malaria parasite. Our ligand-based virtual screening study resulted in the discovery of novel PfSUB1 inhibitors. Further lead optimization of these compounds, to improve binding affinity in the nanomolar range, may promote them as drug candidates. In this thesis we postulate that the accuracy of computational tools in drug discovery may be enhanced to take advantage of the exponential increase of experimental data and the availability of cheaper computational power such as cloud computing.

The overall aim of this thesis was to describe pregnant women's and partners' views and experiences on early prenatal screening with the combined test, with special focus on the two-step information model. Interviews were performed with 15 couples who had taken part in the extended information visit about prenatal screening, describing their perceptions of the information model (I) and ten couples or women of those, for a follow-up interview exploring their decision-making process (II). Seven couples, who had not taken part in the extended information visit, were interviewed describing their views and experiences about prenatal screening (III). A questionnaire was answered by 295 women and by 223 partners about their satisfaction about the decision whether or not to participate in the combined test, and their assessment of whether or not this choice had been difficult (IV). The results showed that different opinions were expressed about the offer of the extended information visit. The separate visit was welcomed by most couples (I). The decision-making process regarding whether to take part in the test or not was described by most couples as a fairly straightforward decision, while for others it was a more complex process that required a great deal of consideration (II). An apprehension of the test, by some of those who had refrained the extended information visit, was that it was an expression of society's involvement in decisions that belong to the expectant parents (III). Ninety-three percent of both women and partners considered the decision about participating in the combined tests as uncomplicated, and well over 90%, of both women and partners were satisfied with their decision (IV). The conclusions in this thesis, are that the decision whether or not to participate in the combined test is multidimensional and influenced by different views. The two-step information model helped the pregnant woman and the partner to make a decision in a fairly straightforward process or a more complex process with mixed feelings.