Feasibility, validity and acceptability of self-collected samples for human papillomavirus (HPV) testing in rural Malawi

AimThe World Health Organization (WHO) recently endorsed human papillomavirus (HPV) testing as a cervical cancer screening method in countries without established programs. Self-collection for HPV testing may be an effective way to expand screening. Our objective was to assess the feasibility, validity, and acceptability of self-collection for HPV testing in a population of care-seeking, unscreened women in rural Malawi.MethodsWe enrolled women reporting to a rural Malawian clinic from January to August 2015. Participants were offered the option to self-collect a vaginal sample and the study clinician collected a cervical sample for HPV testing. Using the clinician-collected sample as the reference standard, we calculated a kappa statistic, sensitivity, and specificity by hr-HPV type. Participants also received a brief survey assessing acceptability of the procedure.ResultsAmong the 199 enrolled women, 22% had any high risk-HPV. Comparing self- and clinician-collected samples for HPV testing, we found generally high agreement (κ = 0.66-0.90) and high specificity (98%-100%), but varied sensitivity (50%-91%) for different types of hr-HPV. We also found that self-collection was acceptable, with 98% of women reporting it was easy to do and 99% reporting willingness to do so again.ConclusionsWHO guidelines recommend that treatment is available immediately after a positive screening test for clinic-based cervical cancer screening programs. Our findings demonstrate that self-collection of samples for HPV testing is a feasible and acceptable method of cervical cancer screening in this rural Malawian population. High agreement between the self- and clinician-collected samples and high levels of acceptability among women in the study suggest that self-collection of vaginal samples for HPV testing may be effectively incorporated into screening programs among rural, largely unscreened populations

Surface evolution during crystalline silicon film growth by low-temperature hot-wire chemical vapor deposition on silicon substrates

We investigate the low-temperature growth of crystalline thin silicon films: epitaxial, twinned, and polycrystalline, by hot-wire chemical vapor deposition (HWCVD). Using Raman spectroscopy, spectroscopic ellipsometry, and atomic force microscopy, we find the relationship between surface roughness evolution and (i) the substrate temperature (230–350 °C) and (ii) the hydrogen dilution ratio (H2/SiH4=0–480). The absolute silicon film thickness for fully crystalline films is found to be the most important parameter in determining surface roughness, hydrogen being the second most important. Higher hydrogen dilution increases the surface roughness as expected. However, surface roughness increases with increasing substrate-temperature, in contrast to previous studies of crystalline Si growth. We suggest that the temperature-dependent roughness evolution is due to the role of hydrogen during the HWCVD process, which in this high hydrogen dilution regime allows for epitaxial growth on the rms roughest films through a kinetic growth regime of shadow-dominated etch and desorption and redeposition of growth species

Who are the Jordanians? The Citizen-Subjects of Abdullah II

Who are the Jordanians? This dissertation approaches this question from the position of how: how is Jordanian citizenship thought of and practiced? As such this is not a study of national identity, but of citizenship. Al-sh’ab yureed…Much has been said about this clarion call which echoed in streets and squares across the Arab world in 2011/2012. Jordanians shared with their regional co-demonstrators a basis on which their claims, regardless of substantive differences, were made: citizenship. However actual examinations of citizenship since remain limited, beyond conceiving it as little more than a status of belonging. The thesis beyond is an investigation into the practice and theory of Jordanian citizenship. Divided into three parts and six chapters, the thesis makes several principal arguments. Part one: Citizens and Subjects? Theorising on History consists of the first three chapters. It establishes what I mean when speaking of a citizenship approach. It is advanced that citizenship’s historical pedigree in an Anglo-European context does not correlate with its Arabic counterparts. This becomes problematic when Anglo-European assumptions influence approaches to citizenship in the Arab world. Hence the need to elucidate the historical development of jinsiyyah and muwātanah. Third, this development is contextualised within Jordanian political history. The historical construction of Jordanian citizenship is situated in its contemporary context since the ascension of Abdullah II in 1999. Part two: Citizenship in Contemporary Jordan, containing chapters four, and five. Chapter four, making use of fieldwork conducted in Jordan uses contemporary reflections on citizenship from Jordanians as a lens through which the first decade of Abdullah II’s reign is analysed. A key characteristic of citizenship’s theory and practice is highlighted: the absence of accountability and ownership. The thesis then provides analysis of the 2011/2012 uprisings, situating them as a citizen search for ownership and accountability. Part three: Practices Within and Between Jinsiyyah and Muwātanah, is composed of chapters six, seven and eight, with a focus on contemporary affairs in the Jordan. Three areas: the gendering of citizenship, the politics of citizen expression and the intersections between tribalism and citizenship, are explored

Engineering assessment of current and future vehicle technologies, FMVSS No. 121, Air brake systems, Final report.

National Highway Traffic Safety Administration, Washington, D.C.http://deepblue.lib.umich.edu/bitstream/2027.42/57494/1/100608.pd

Mitochondrial Calcium Changes in Sheared Human Vascular Endothelial Cells

Endothelial cells are subjected to various forces and stresses causing physiological reactions to occur. Changes in cytosolic and mitochondrial calcium due to shear forces/stresses are required to maintain homeostasis of the cell. Monitoring these changes are vital to scientific research and are done using fluorophores. Human umbilical vein endothelial cells (HUVECs) were subjected to two fluorophores with different excitation and emission wavelengths, Fluo-4 and Rhod-2. While examining collected data, it was noted that during a static baseline recording, premature excitation of Fluo-4 fluorescence was being experienced by some cells. The cause of this excitation was phototoxicity, a result of light exposure. A static baseline was conducted using only Fluo-4 in which no phototoxicity was experienced. An experiment was then analyzed using MATLAB comparing the fluorescence over time in cells that used both Fluo-4 and Rhod-2. It was shown that early fluorescence was occurring in multiple cells as well as an overall decrease in fluorescence over time, indicating photobleaching. These results indicated that Rhod-2 was causing the photoactivation of fluorophores. Previous studies potentially explain the mechanism to be an increase in radical oxidative species (ROS) which activate the inositol 1,4,5-trisphosphate receptor. Further studies will be conducted without the use of Rhod-2 and instead will use an adenovirus to transfect cells.No embargoAcademic Major: Biomedical Engineerin

Mise en évidence et caractérisation d'une spécificité anticorps "TcCRA" chez l'homme

Cross-reactive antibodies are characterized by their recognition of antigens that are different from the trigger immunogen. This happens when the similarity between two different antigenic determinants becomes adequate enough to enable a specific binding. Here, we report for the first time the presence, at an ‘‘abnormal’’ high frequency in blood samples from French human subjects, of antibodies that cross-react with a protein of Trypanosoma cruzi. We called these antibodies ‘‘Trypanosoma cruzi Cross-Reactive Antibodies’’ or TcCRA. Our findings show a large seroprevalence of cross-reactive antibodies and suggest that they are induced by a widely spread immunogen, acquired during childhood. Furthermore TcCRA serology does not seem to be associated with commonly known pathogens in clinical routine. Our hypothesis of the implication of a viral agent in the induction of TcCRA was further put forward when we documented a seroconversion pattern in a patient after allogenic stem cell transplantation. This initial exploratory work will serve as the basis for organizing prospective and retrospective clinical investigations, where we will pursue the analysis of TcCRA in order to elucidate its etiology and clinical importanceLes anticorps à réactivité croisée sont caractérisés par leur capacité à reconnaitre des épitopes différents de ceux qui ont causé leur induction. Cela se produit lorsque des similitudes structurales entre les deux déterminants antigéniques deviennent suffisantes pour permettre une liaison spécifique. Nous rapportons ici pour la première fois la présence, à une haute fréquence, d'anticorps dans des échantillons de sang provenant de sujets vivant en France avec une protéine de Trypanosoma cruzi. Nous avons appelé ces anticorps ''Trypanosoma cruzi Cross-reactive antibodies'' ou TcCRA. Nos résultats montrent une forte séroprévalence des anticorps à réaction croisée, suggérant qu'ils sont induits par un immunogène largement répandu, acquis dès l’enfance et qui ne semble pas être associé à des agents pathogènes communs en clinique humaine. Les recherches effectuées in silico orientent vers un virus de la famille des Herpesviridae. Cette hypothèse est renforcée par la documentation d’un profil sérologique de séroconversion chez un patient qui a subi une transplantation de cellules souches allogéniques. Ce premier travail va servir de base à la mise en oeuvre d’investigations cliniques rétrospectives et prospectives destinées à élucider l’étiologie et l’importance clinique du biomarqueur TcCR

Charakterisierung des autonomen Nervensystems in Ruhe sowie unter Stresseinwirkung bei Patienten mit Rheumatoider Arthritis

Eine Dysregulation neuro-immunologischer Interaktionen und eine veränderte Stressantwort werden als Teil der Pathogenese der Rheumatoiden Arthrtitis (RA) diskutiert. Dabei könnte eine autonome Dysfunktion eine wichtige Rolle spielen. Um dem nachzugehen, wurde an Patienten mit unterschiedlicher Krankheitsaktivität die Aktivität des autonomen Nervensystems in Ruhe und in Reaktion auf minor Stress sowie erstmals deren Assoziation zu Gen-Polymorphismen β2- adrenerger Rezeptoren (β2ARs), welche sich u.a. auf Immunzellen befinden, untersucht. Zur Bestimmung autonomer Aktivität wurde an 112 RA- und 48 Osteoarthrose-Patienten die sympathische Hautantwort (SSR) sowie die Herzratenvariabilität (HRV) getestet. Standardisierte Stresstests kamen zur Anwendung. Eine Allel-spezifische Polymerase-Ketten-Reaktion diente zur Ermittlung der Varianten des β2ARs an Aminosäureposition 16, 27 und 164. Es konnte gezeigt werden, dass die autonome Aktivität bei RA in Ruhe durch eine signifikant erhöhte Herzfrequenz, ein Überwiegen des Sympathikus im Verhältnis zum Parasympathikus sowie eine signifikant erniedrigte Parasympathikusaktivität gekennzeichnet ist. Die Stressantwort bei RA war signifikant häufiger pathologisch als bei der Kontrollgruppe und durch signifikante Hypoaktivität und Hyporeaktivität des Parasympathikus sowie eine signifikant erniedrigte HRV charakterisiert. Das Zusammenspiel beider Schenkel des ANS erschien gestört. Die SSR-Werte befanden sich im Normbereich. Schlechtere Werte waren jedoch signifikant mit hohem CRP assoziiert. Desweiteren war Heterozygotie an allen Gen-Positionen der β2ARs signifikant mit RA assoziiert. Gln27Gln (signifikant häufiger für Gesunde) ging mit signifikant niedrigerer Krankheitsaktivität einher. Starkes Überwiegen des SNS in Ruhe sowie niedrige parasympathische Aktivität (HRV-Daten) waren signifikant mit hoher Krankheitsaktivität assoziiert. Zusammenfassend weist die vorliegende Arbeit auf eine autonome Dysregulation bei Patienten mit RA hin, was mit klinischen Parametern der RA assoziiert war. Weiterhin unterstreicht die Studie die Assoziation von β2AR Polymorphismen mit einer RA und liefert einen weiteren Beitrag zum Verständnis der Pathogenese dieser Erkrankung

Effets des modulateurs du récepteur de la progestérone dans des modèles de cancer mammaire humain

The role of progestins and the progesterone receptor (PR) in breast tumorigenesis has now been elucidated. PR is expressed as two isoforms PRA and PRB, differing by their structure and their transcriptional activity. They are often co-expressed in normal breast tissue but the predominance of PRA expression is associated with mammary carcinogenesis, a bad prognosis and an endocrine-resistance. Antiprogestins inhibit mammary tumor growth in several experimental models. The aim of this thesis was to investigate the effect of a well-known selective PR modulator (SPRM), Ulipristal acetate (UPA) in two complementary breast cancer models. In vitro, we used the newly established bi-inducible breast cancer cell line “MDA-iPRAB”, and demonstrated an anti-proliferative activity of UPA in progesterone-dependent, PRA-specific MDA-iPRAB cell proliferation. We also studied the expression of PRA-target genes involved in mammary tumorigenesis, and showed a correlation between cell proliferation and the expression of the anti-apoptotic factor BCL2-L1 (transcript and protein). The transcriptional activation of BCL2-L1 was stimulated by the progesterone in MDA-iPRA cell line, inhibited by UPA and was associated with a specific and selective recruitment of PRA to BCL2-L1 regulatory regions (ChIP assays). In vivo, we evaluated the anti-tumoral activity of UPA and a new class of selective and passive progesterone receptor antagonist ‘APRns' in patient-derived breast cancer xenograft in nude mice. UPA slowed down mammary tumor growth, decreased cell proliferation (Ki67, PCNA) and inhibited the BCL2-L1 expression. Further investigation are needed to determine the actions of APRns. In summary, UPA has an antiproliferative and a pro-apoptotic activities, which suggests a potential interest of UPA in breast cancer endocrine therapy.Le rôle des progestatifs et du récepteur de la progestérone (PR) dans la carcinogénèse mammaire est maintenant établi. Le PR est exprimé sous deux isoformes PRA et PRB dont l'expression est équimolaire mais qui différent par leur activité transcriptionnelle des gènes cibles. La surexpression de PRA est associée à un pronostic défavorable du cancer mammaire, et est observée chez les femmes à haut risque génétique de cancer du sein. L'utilisation d'antagonistes pour inhiber l'activité de PR pourrait constituer une stratégie thérapeutique potentielle. L'objectif de cette thèse a été d'évaluer les effets de l'ulipristal acétate (UPA), un anti-progestatif, sur la tumorigenèse mammaire dans deux modèles d'études complémentaires. In vitro, dans la lignée cancéreuse mammaire bi-inductible (MDA-iPRAB) développée au laboratoire. Nous avons démontré qu'UPA inhibe la prolifération cellulaire induite par la progestérone en présence de PRA. L'expression de certains gènes clés de la tumorigenèse mammaire, cibles de PRA a été étudiée. Une corrélation entre avec la prolifération cellulaire et l'expression du facteur anti-apoptotique BCL2-L1 (messager et protéine) a été démontrée. L'activation transcriptionnelle, dépendante de la progestérone et inhibée par l'UPA, s'accompagne d'un recrutement spécifique et sélectif de PRA sur des séquences régulatrices du gène BCL2-L1, comme le démontrent les expériences de ChIP. In vivo, nous avons évalué l'efficacité anti-tumorale de l'UPA ainsi qu'une nouvelle classe d'antagoniste sélective et passive de PR, les « APRns » dans un modèle murin de xénogreffe de tumeur mammaire humaine HBCx34. UPA ralentit la croissance tumorale, diminue la prolifération cellulaire (Ki67, PCNA) et inhibe l'expression de BCL2-L1. L'ensemble de nos résultats démontrent une action antiproliférative et apoptotique de l'UPA ce qui suggère une utilisation potentielle d'antagonistes de PR dans la prise en charge du cancer du sein