Ultrasound in the management of women with post-menopausal bleeding

The aim of this thesis was to investigate how ultrasound can be used in the diagnostic work-up of women with post-menopausal bleeding (PMB) to optimise and individualise their management. The thesis is based on six studies comprising post-menopausal women with (Study I-VI) and without (Study VI) abnormal bleeding. The clinical value of conventional ultrasound, with or without saline infusion (hydrosonography), and of power Doppler ultrasound, was determined, and the performance of different endometrial biopsy techniques was compared and correlated with sonographic findings. Re-bleeding and endometrial growth were common during a follow-up period of 12 months in women with PMB and endometrium /= 5 mm. If these women are managed by ultrasound follow-up, endometrial sampling should be performed if the endometrium grows to a thickness of >/= 5 mm, and perhaps also in cases of re-bleeding. Endorette® (a simple endometrial sampling device) and D&C had similar diagnostic value in women with PMB and endometrium /= 7 mm. However, in another study on women with PMB and endometrium >/= 5 mm, we found that D&C failed to diagnose about half of the focal lesions in the uterine cavity that were removed by operative hysteroscopy. Thus, the presence or absence of focal lesions should determine the diagnostic procedure. Hydrosonography was found to be as good as hysteroscopy with regard to detecting focal lesions, but neither method was accurate enough in discriminating benign from malignant lesions. Distension difficulties at hydrosonography were more common in women with endometrial cancer and should therefore raise a suspicion of malignancy. A multivariate logistic regression model including clinical information, conventional ultrasound variables, and power Doppler variables seems to be superior to endometrial ultrasound morphology in correctly diagnosing endometrial cancer in cases where the endometrium measures 5-15 mm. The reproducibility of endometrial measurements allows reliable discrimination between post-menopausal women with endometrium /= 5 mm

Polymerizing the fibre between bacteria and host cells: the biogenesis of functional amyloid fibres

Amyloid fibres are proteinaceous aggregates associated with several human diseases, including Alzheimer's, Huntington's and Creutzfeldt Jakob's. Disease-associated amyloid formation is the result of proteins that misfold and aggregate into β sheet-rich fibre polymers. Cellular toxicity is readily associated with amyloidogenesis, although the molecular mechanism of toxicity remains unknown. Recently, a new class of ‘functional’ amyloid fibres was discovered that demonstrates that amyloids can be utilized as a productive part of cellular biology. These functional amyloids will provide unique insights into how amyloid formation can be controlled and made less cytotoxic. Bacteria produce some of the best-characterized functional amyloids, including a surface amyloid fibre called curli. Assembled by enteric bacteria, curli fibres mediate attachment to surfaces and host tissues. Some bacterial amyloids, like harpins and microcinE492, have exploited amyloid toxicity in a directed and functional manner. Here, we review and discuss the functional amyloids assembled by bacteria. Special emphasis will be paid to the biology of functional amyloid synthesis and the connections between bacterial physiology and pathology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75549/1/j.1462-5822.2008.01148.x.pd

Assembly, Spatial Distribution, and Secretion Activity of the Curlin Secretion Lipoprotein, CsgG.

Escherichia coli assembles functional amyloid fibers called curli. Produced by many Enterobacteriaceae spp., curli fibers are associated with biofilm formation, host cell adhesion and invasion, and immune system activation. CsgB nucleates the major curli subunit protein, CsgA, into a self-propagating amyloid fiber on the cell surface. CsgA and CsgB cell surface association and subsequent fiber polymerization are efficient processes, yet little is known about how the subunits reach and become positioned on the surface. I have characterized the role of CsgG in curli subunit secretion across the outer membrane, and found that CsgG is the central molecule of the curli secretion and assembly complex. CsgG formed an oligomeric complex in the outer membrane that interacted with at least three other csg encoded proteins. I found that the CsgG lipoprotein spanned the outer membrane, was sufficient for curlin transport across the outer membrane, and that a specific signal peptide on the N-terminus of the major fiber subunit directed protein secretion via the CsgG secretion apparatus. I also discovered that CsgG was non-uniformly distributed on the surface of curli-producing cells, and that the assembly, spatial organization, and secretion activity of CsgG was modified by other components of the curli assembly machine. One of the other curli assembly proteins, CsgE, was found to specifically function in the secretion pathway and to modulate both the secretion activity of CsgG and to act directly on CsgA to prevent self-polymerization. These results suggest a model where secretion and fiber assembly are tightly coupled and highly ordered processes.Ph.D.Molecular, Cellular, and Developmental BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/61667/1/emashman_1.pd

Travel-associated hepatitis A in Europe, 2009 to 2015.

BackgroundTravel to countries with high or intermediate hepatitis A virus (HAV) endemicity is a risk factor for infection in residents of countries with low HAV endemicity. Aim: The objective of this study was to estimate the risk for hepatitis A among European travellers using surveillance and travel denominator data. Methods: We retrieved hepatitis A surveillance data from 13 European Union (EU)/ European Economic Area (EEA) countries with comprehensive surveillance systems and travel denominator data from the Statistical Office of the European Union. A travel-associated case of hepatitis A was defined as any case reported as imported. Results: From 2009 to 2015, the 13 countries reported 18,839 confirmed cases of hepatitis A, of which 5,233 (27.8%) were travel-associated. Of these, 39.8% were among children younger than 15 years. The overall risk associated with travel abroad decreased over the period at an annual rate of 3.7% (95% confidence interval (CI): 0.7-2.7) from 0.70 cases per million nights in 2009 to 0.51 in 2015. The highest risk was observed in travellers to Africa (2.11 cases per million nights). Cases more likely to be reported as travel-associated were male and of younger age (< 25 years). Conclusion: Travel is still a major risk factor for HAV infection in the EU/EEA, although the risk of infection may have slightly decreased in recent years. Children younger than 15 years accounted for a large proportion of cases and should be prioritised for vaccination

Simple ultrasound rules to distinguish between benign and malignant adnexal masses before surgery: prospective validation by IOTA group

Objectives To prospectively assess the diagnostic performance of simple ultrasound rules to predict benignity/malignancy in an adnexal mass and to test the performance of the risk of malignancy index, two logistic regression models, and subjective assessment of ultrasonic findings by an experienced ultrasound examiner in adnexal masses for which the simple rules yield an inconclusive result

Archetype analysis in sustainability research : meanings, motivations, and evidence-based policy making

Archetypes are increasingly used as a methodological approach to understand recurrent patterns in variables and processes that shape the sustainability of social-ecological systems. The rapid growth and diversification of archetype analyses has generated variations, inconsistencies, and confusion about the meanings, potential, and limitations of archetypes. Based on a systematic review, a survey, and a workshop series, we provide a consolidated perspective on the core features and diverse meanings of archetype analysis in sustainability research, the motivations behind it, and its policy relevance. We identify three core features of archetype analysis: recurrent patterns, multiple models, and intermediate abstraction. Two gradients help to apprehend the variety of meanings of archetype analysis that sustainability researchers have developed: (1) understanding archetypes as building blocks or as case typologies and (2) using archetypes for pattern recognition, diagnosis, or scenario development. We demonstrate how archetype analysis has been used to synthesize results from case studies, bridge the gap between global narratives and local realities, foster methodological interplay, and transfer knowledge about sustainability strategies across cases. We also critically examine the potential and limitations of archetype analysis in supporting evidence-based policy making through context-sensitive generalizations with case-level empirical validity. Finally, we identify future priorities, with a view to leveraging the full potential of archetype analysis for supporting sustainable development

Higher D or Li: Probes of Physics beyond the Standard Model

Standard Big Bang Nucleosynthesis at the baryon density determined by the microwave anisotropy spectrum predicts an excess of \li7 compared to observations by a factor of 4-5. In contrast, BBN predictions for D/H are somewhat below (but within ~2 \sigma) of the weighted mean of observationally determined values from quasar absorption systems. Solutions to the \li7 problem which alter the nuclear processes during or subsequent to BBN, often lead to a significant increase in the deuterium abundance consistent with the highest values of D/H seen in absorption systems. Furthermore, the observed D/H abundances show considerable dispersion. Here, we argue that those systems with D/H \simeq 4 \times 10^{-5} may be more representative of the primordial abundance and as a consequence, those systems with lower D/H would necessarily have been subject to local processes of deuterium destruction. This can be accounted for by models of cosmic chemical evolution able to destroy in situ Deuterium due to the fragility of this isotope.Comment: 22 pages, 8 figure