Efficiently Tracking Homogeneous Regions in Multichannel Images

We present a method for tracking Maximally Stable Homogeneous Regions (MSHR) in images with an arbitrary number of channels. MSHR are conceptionally very similar to Maximally Stable Extremal Regions (MSER) and Maximally Stable Color Regions (MSCR), but can also be applied to hyperspectral and color images while remaining extremely efficient. The presented approach makes use of the edge-based component-tree which can be calculated in linear time. In the tracking step, the MSHR are localized by matching them to the nodes in the component-tree. We use rotationally invariant region and gray-value features that can be calculated through first and second order moments at low computational complexity. Furthermore, we use a weighted feature vector to improve the data association in the tracking step. The algorithm is evaluated on a collection of different tracking scenes from the literature. Furthermore, we present two different applications: 2D object tracking and the 3D segmentation of organs.Comment: to be published in ICPRS 2017 proceeding

Subtyping of Patients with Primary Aldosteronism: An Update

Primary aldosteronism (PA) comprises two main subtypes: unilateral aldosteronism, mainly caused by aldosterone-producing adenoma;and bilateral adrenal hyperplasia. Establishing the correct subtype in patients with PA is indispensible for choice of treatment. In addition to established methods, alternative tests are evolving for subtyping. Computed tomography (CT) and adrenal venous sampling (AVS) are currently recommended in the guidelines for the diagnostic work-up of patients with PA. CT cannot be used as a stand-alone test for subtyping because of its limited accuracy but may be used in combination with other tests such as AVS or functional imaging. Nevertheless CT remains mandatory to exclude adrenocortical carcinoma. AVS provides the most accurate test to detect excessive secretion of aldosterone from an adrenal mass but has several practical limitations and disadvantages. Therefore, alternative non-invasive and patient-friendly methods are required to determine the need for adrenalectomy. Functional imaging with specific molecular positron emission tomographic ligands is a potential alternative method that may replace AVS for subclassifying patients with PA. The results of preliminary studies of C-11-metomidate are promising but ligands incorporating radionuclides with longer half-lives that selectively bind to CYP11B2 are needed. Steroid profiling provides another method for subtyping and selecting patients for adrenalectomy, but this technology is in its infancy and prospective outcome-based studies are required to determine if this technique may provide an alternative to AVS

New and refined tools and guidelines to expand the scope and improve the reproducibility of palaeomicrobiological research

Microorganisms vastly outnumber animals and play key roles in our planet’s biosphere. Recent advances in technology and computational tools have made it possible to study the great diversity of microorganisms on Earth rapidly and efficiently. A large fraction of this research has focused on the microbial communities that inhabit the human body—the human microbiota—which account for more than half of the cells we carry and collectively possess >100-fold more genes than the human genome. This research has discovered key coevolutionary relationships between the host and microbiota, many of which have been shaped through human history to the benefit of both partners. Evidence is mounting that disruptions to these microbial communities and to the relationship between the host and microbiota (dysbioses) can have a drastic effect on human health. There is also evidence that recent changes in human societies, such as antibiotic use and exposure to bioactive chemicals, have promoted dysbiosis to the detriment of human wellbeing. Thus, there is great interest in studying human microbiota that existed prior to these recent changes, with the hope of providing insight into the evolution of the human microbiota and informing modern medical strategies and the development of new therapies. The recent finding that ancient microbial DNA is preserved in human dental calculus (calcified dental plaque) offers us the ability to investigate how oral microbiota have changed through human history. Additionally, further advances in DNA sequencing technology and laboratory methods have made it possible to rapidly process ancient specimens and to obtain large quantities of ancient microbial data. However, our ability to analyse this data has not caught up with the speed at which we generate it, and there are many analytical challenges and pitfalls that stand in the way of realising the full potential of ancient microbial DNA studies. This thesis aims to develop and improve methods for analysing ancient microbial DNA and to identify and highlight challenges and pitfalls present in the field in order to increase the quality of future research. Initially, I propose a novel approach of using ancient microbial DNA in dental calculus as a proxy for determining past human migrations. Next, I develop and propose criteria to improve research standards in low-biomass microbiota research. I then assess how characteristics of ancient DNA impact our ability to determine the composition of past microbiota and develop new analytical strategies and methods to improve current taxonomic identification approaches. I also generate and authenticate high-quality data for 132 new ancient dental calculus samples from the Asia-Pacific region, and develop and test two new methods to analyse this data and determine if oral microbiota can be used to infer past human migration and demographic history. Finally, I critically review and respond to three questionable palaeomicrobiological studies with the hope that future researchers, reviewers, and editors will learn from the issues highlighted. Ultimately, this thesis highlights and constructively addresses key pitfalls of palaeomicrobiological research and pushes the field closer to realising its potential.Thesis (Ph.D.) -- University of Adelaide, School of Biological Sciences, 201

Overexpression of the Insulin-like growth factor 1 receptor (IGF-1R) is associated with malignancy in familial pheochromocytomas and paragangliomas

CONTEXT: Pheochromocytomas and paragangliomas (pheo/pgl) are neuroendocrine tumours derived from chromaffin cells. Although mostly benign, up to 26% of pheo/pgl will undergo malignant transformation. Reliable histological signs to differentiate benign pheo/pgl from malignant tumours are currently lacking. Increased IGF-1R expression has been shown during progression to metastatic phenotypes of several types of cancer. OBJECTIVE: To analyse the distribution and expression of the IGF-1R in pheo/pgl of different genetic origin and degree of malignancy. MEASUREMENTS: We studied the expression of the IGF-1R protein by immunohistochemistry, in 40 primary tumours from patients with pheo/pgl from different genetic aetiology (11 of 29 metastatic/nonmetastatic diseases). RESULTS: We found a strong association between increased expression of IGF-1R and malignant behaviour regardless of the age at diagnosis and the genetic aetiology. IGF-1R labelling was mostly weak in primary tumours from patients with nonmetastatic pheo/pgl. Conversely, intense IGF-1R labelling was predominant in cases of pheo/pgl with confirmed metastatic disease. The risk of metastases was 11·7 times higher if tumour IGF-1R labelling was intense independently of age at diagnosis. The probability of remaining free of metastases was higher in patients with pheo/pgl scored weak for IGF-1R at 60 months and more than twofold higher at 120 months of follow-up than in patients with intense IGF-1R labelling in their primary tumours. CONCLUSIONS: Our results strongly suggest that IGF-1R is associated with malignancy in familial pheo/pgl and that IGF-1R expression in the primary tumour might be a useful tool to detect those patients harbouring pheo/pgl who have an increased risk of metastasis.Fil: Fernández, María Celia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Martin, Ayelen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Venara, Marcela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Calcagno, María Lujan. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Sanso, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Quintana, Silvina. Instituto de Análisis Farestaie; ArgentinaFil: Chemes, Hector Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Barontini, Marta Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Pennisi, Patricia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentin

Biochemical Diagnosis of Catecholamine-Producing Tumors of Childhood: Neuroblastoma, Pheochromocytoma and Paraganglioma

Catecholamine-producing tumors of childhood include most notably neuroblastoma, but also pheochromocytoma and paraganglioma (PPGL). Diagnosis of the former depends largely on biopsy-dependent histopathology, but this is contraindicated in PPGL where diagnosis depends crucially on biochemical tests of catecholamine excess. Such tests retain some importance in neuroblastoma though continue to largely rely on measurements of homovanillic acid (HVA) and vanillylmandelic acid (VMA), which are no longer recommended for PPGL. For PPGL, urinary or plasma metanephrines are the recommended most accurate tests. Addition of methoxytyramine to the plasma panel is particularly useful to identify dopamine-producing tumors and combined with normetanephrine also shows superior diagnostic performance over HVA and VMA for neuroblastoma. While use of metanephrines and methoxytyramine for diagnosis of PPGL in adults is established, there are numerous pitfalls for use of these tests in children. The establishment of pediatric reference intervals is particularly difficult and complicated by dynamic changes in metabolites during childhood, especially in infants for both plasma and urinary measurements, and extending to adolescence for urinary measurements. Interpretation of test results is further complicated in children by difficulties in following recommended preanalytical precautions. Due to this, the slow growing nature of PPGL and neglected consideration of the tumors in childhood the true pediatric prevalence of PPGL is likely underappreciated. Earlier identification of disease, as facilitated by surveillance programs, may uncover the true prevalence and improve therapeutic outcomes of childhood PPGL. For neuroblastoma there remain considerable obstacles in moving from entrenched to more accurate tests of catecholamine excess

Thromboembolism after metastases in the central nervous system of gynecological cancers: a retrospective analysis in the Ernst-von-Bergmann Klinikum Potsdam

Sowohl aufgrund ihrer Haupterkrankung als auch aufgrund weiterer Morbiditäten und der Behandlungsregimes sind Tumorpatienten gegenüber dem Risiko einer Thrombose oder Embolie besonders exponiert. Dies gilt umso mehr für Patienten mit Fernmetastasen im Zentralnervensystem, jedoch besteht zu möglichen Präventionsansätzen für Thrombosen und Embolien bei dieser Patientengruppe kaum eine Datengrundlage, wobei insbesondere die Berichte für Patientinnen mit gynäkologischen Tumoren unzureichend sind. Aufgrund dessen wurden im Rahmen der vorliegenden Untersuchung klinisch-pathologische (Diagnose, Mobilität, Anzahl und Lokalisation der Metastasen) sowie laborchemische Parameter (Quick, Thrombozytenzahl, Fibrinogenspiegel, C-reaktives Protein) ausgewertet, um das individuelle Thromboserisiko retrospektiv nachvollziehen zu können. Insgesamt wurden die Daten von 260 Patientinnen in einem Alter von durchschnittlich 69,2Jahren (± 11,5 Jahren) ausgewertet. Dabei zeigte sich, dass das Thromboserisiko nicht von der Lokalisation der Tumoren abhängig ist. Ebenfalls konnte kein Einfluss der Metastasenanzahl oder -lokalisation nachgewiesen werden. Gleiches gilt für den Mobilitäts- und neurologischen Status der Patientinnen. Demgegenüber war das Auftreten von Thrombosen statistisch signifikant mit erhöhten Laborparametern für die Thrombozytenanzahl (p < 0,001), sowie signifikant mit den Fibrinogenspiegeln (p=0,023) assoziiert. Die Multivariate Untersuchung ergab nur noch für die Thrombozatenzahl eine signifikante Korrelation bei einer Power von 0.98892 Insbesondere aufgrund der geringen Fallzahlen in der Subgruppenanalyse (Tumor- und Metastasenlokalisation) sind weitere Untersuchungen notwendig, um Prädiktoren für das patientenindividuelle Thromboserisiko im Falle gynäkologischer Tumoren mit Fernmetastasen zu identifizieren und zu etablieren.  Cancer patients are particularly exposed to the risk of thrombosis or embolism due to both their main disease and other morbidities as well as treatment regimens. This applies especially to patients with distant metastases in the central nervous system, but there is hardly any data on possible prevention approaches for thrombosis and embolism in this patient group, in particular the reports for patients with gynecological cancers being inadequate. As a result in the present study pathologic (diagnosis, mobility, number and location of the metastases) as well as laboratory parameters (Quick, platelet count, fibrinogen level, C-reactive protein) were evaluated retrospectively in order to examine the individual thrombosis risk. Overall the data from 260 patients with an average age of 69.2 years (± 11.5 years) were evaluated. It could be shown that the risk of thrombosis does not depend on the cancer localization. Also no influence of metastasis number or localization could be found. The same applies to the mobility and neurological status of the patients. In contrast, the incidence of thrombosis was statistically significantly associated with increased platelet number laboratory parameters (p < 0.001), and significantly with fibrinogen level (p=0,023). The multivariate analysis then only showed significance for the correlation with platelet numbers with a power of 0.98892. In particular due to the low number of cases in the subgroup analysis (cancer and metastasis localization) further investigations are necessary to identify and establish predictors for the patient-specific risk of thrombosis in the case of gynecological cancers with distant metastases