Personalized prostate cancer management : AI-assisted prostate pathology and improved active surveillance

Prostate cancer is a major global health concern and is the most common cancer-related cause of death in Sweden. Prostate cancer screening using PSA has been shown to reduce prostate cancer mortality but also leads to significant overdiagnosis and overtreatment of low-risk cancers. Improved risk stratification and effective active surveillance are crucial to balancing the benefits of screening with the risk of overdiagnosis and overtreatment. In Study I, we studied the uptake and the follow-up of active surveillance using a retrospective cohort of patients who were diagnosed with low-risk prostate cancer between 2008 and 2017 in Stockholm County. Our results showed that only 50% of eligible active surveillance patients received active surveillance as their primary treatment choice at diagnosis. Most men that enrolled in active surveillance remained on surveillance during the first years after diagnosis (82% during a median 3.5 years), but did not receive a follow up according to guidelines with regard to repeat biopsies and PSA tests. Current clinical practice has seen an increase in the use of magnetic resonance imaging (MRI) and the incorporation of risk prediction models to select men with the highest suspicion of clinically significant prostate cancer for prostate biopsy. However, the effectiveness and how MRI and risk prediction models should be incorporated into active surveillance follow-up have yet to be established. Study II evaluated the performance of MRI-targeted biopsies and a blood-based risk prediction model (the Stockholm3 test) for monitoring disease progression in patients on active surveillance and compared this to the conventional follow-up using PSA and systematic biopsies. When MRI-targeted and systematic biopsies were combined, the detection rate of clinically significant prostate cancer increased when compared to conventional systematic biopsies. Biopsies performed in MRI-positive men resulted in a 49% reduction in performed biopsies, at the expense of failing to diagnose 1.4% clinically significant prostate cancer in MRInegative men. The incorporation of the Stockholm3 test showed a 27% reduction in required MRI investigations and a 57% reduction in performed biopsies compared to performing only systematic biopsies. In Study III, we digitized biopsy cores from STHLM3 participants to develop an artificial intelligence (AI) for prostate cancer diagnostics. The AI system demonstrated clinically useful performance that was comparable to that of the study pathologist for cancer detection (AUC of 0.986) and for predictions of cancer length (correlation of 0.87) and grading performance that was on par with that of expert prostate pathologists. In Study IV, we developed a conformal predictor to estimate the uncertainty of the predictions for the model in Study III. The uncertainty estimates were used to control the error rate so that only predictions with high confidence are accepted and unreliable predictions can be detected. The conformal predictor was able to identify unreliable predictions as a result of variations in digital pathology scanners, preparation of tissue in different pathology laboratories, and the existence of unusual prostate tissue that the AI model was not exposed to during training. Little is known about the relationships between prostate cancer genetic risk factors and the morphology of prostate tissue. In Study V:, we investigated whether weakly supervised deep learning can learn to detect such possible associations. The findings in this paper imply relationships between prostatic tissue morphology and genetic risk factors for prostate cancer, particularly in young men. These results provide proof of principle for exploring the use of morphological information in multi-modal prostate cancer risk prediction algorithms. In conclusion, the purpose of this thesis was to describe possible extensions to improve prostate cancer active surveillance management, as well as to develop prediction models for improved prostate cancer diagnostics

Impact of local information in growing networks

We present a new model of the evolutionary dynamics and the growth of on-line social networks. The model emulates people's strategies for acquiring information in social networks, emphasising the local subjective view of an individual and what kind of information the individual can acquire when arriving in a new social context. The model proceeds through two phases: (a) a discovery phase, in which the individual becomes aware of the surrounding world and (b) an elaboration phase, in which the individual elaborates locally the information trough a cognitive-inspired algorithm. Model generated networks reproduce main features of both theoretical and real-world networks, such as high clustering coefficient, low characteristic path length, strong division in communities, and variability of degree distributions.Comment: In Proceedings Wivace 2013, arXiv:1309.712

Testing reproductive allometry in fish

Abstract Energy allocation models have proved useful for clarifying the ecological mechanisms which influence growth and reproduction schemes in species with indeterminate growth and for understanding how traits correlate with generate the life history of specific species. In view of the need to understand how exploitation affects species for which few data on key population parameters such as reproductive potential and population growth rate are available, it would be helpful if simple energy allocation schemes parametrized by easily obtainable data could be used to estimate parameters such as reproductive effort and output. Testing the predictions of three such models on fecundity data from a range of species, we show how the simplifications required in a generalized energy allocation scheme are reflected in the deviations between model predictions and empirical data, and discuss the validity of the assumptions underlying these models. We caution against over-reliance on generalized and simplified models to predict reproductive effort.</jats:p

Soft nanostructuring of YBCO Josephson Junctions by phase separation

We have developed a new method to fabricate biepitaxial YBa2Cu3O(7-x) (YBCO) Josephson junctions at the nanoscale, allowing junctions widths down to 100 nm and simultaneously avoiding the typical damage in grain boundary interfaces due to conventional patterning procedures. By using the competition between the superconducting YBCO and the insulating Y2BaCuO5 phases during film growth, we formed nanometer sized grain boundary junctions in the insulating Y2BaCuO5 matrix as confirmed by high resolution transmission electron microscopy. Electrical transport measurements give clear indications that we are close to probing the intrinsic properties of the grain boundaries.Comment: 16 pages, 6 figure

Gain curves in depletable food patches: A test of five models with European starlings

A forager's gain curve, the cumulative number of prey harvested from a patch as a function of time spent in the patch, influences optimal patch departure rules and interpretations of patch use data. We describe models of five different search strategies that yield different gain curves. Hence they would influence a forager's decision for patch departure differently and, consequently, how researchers should interpret patch residence times and giving-up densities. However, the models are virtually impossible to separate based on data of the gain curves per se. Therefore, we develop a series of diagnostic tests that can be used to discriminate among models. These tests consider how the instantaneous harvest rate within patches depends on initial (IPD) and current prey density (CPD) and search time. We applied these tests to data collected from European starlings (Sturnus vulgaris) foraging in experimental food patches of known initial prey density. The starlings' harvest rate increased with CPD, an indication of diminishing returns. However, a given CPD yielded a lower instantaneous intake rate the higher the IPD. Thus, the two models most commonly assumed in foraging studies, systematic and random search, can be unequivocally rejected. Instead, we found support for a new model, negative stirring, in which the starlings spoil their own future foraging returns by aggregating the remaining prey items as they search

The interdisciplinary decision problem : Popperian optimism and Kuhnian pessimism in forestry

Interdisciplinary research in the fields of forestry and sustainability studies often encounters seemingly incompatible ontological assumptions deriving from natural and social sciences. The perceived incompatibilities might emerge from the epistemological and ontological claims of the theories or models directly employed in the interdisciplinary collaboration, or they might be created by other epistemological and ontological assumptions that these interdisciplinary researchers find no reason to question. In this paper we discuss the benefits and risks of two possible approaches, Popperian optimism and Kuhnian pessimism, to interdisciplinary knowledge integration where epistemological and ontological differences between the sciences involved can be expected.Peer reviewe

Landscape? Urbanism

I och med Landscape Urbanism har landskapsbegreppet sedan en tid upplevt en hausse inom arkitektur- och stadsbyggnadsdiskurs. I och med denna nya uppmärksamhet för landskapet har ett nytt behov uppstått: att diskutera vad som egentligen menas när man använder detta mångtydiga begrepp. Med detta fokus behandlar denna uppsats komplikationerna som uppstår när ordet landskap och dess ofta motstridiga betydelser används utan att kommunicera vad som avses. Med utgångspunkt i lingvistiska teorier hävdar jag därför att språket och således semantiken, ordens innebörd, är av yttersta vikt för att formulera och konstruera nya stadsbyggnadsteorier såsom Landscape Urbanism. För vad betyder egentligen Landscape inom Landscape Urbanism? Hur kommer det sig att ordet dels används för att referera till ytorna ”mellan husen”, men även används som ett begrepp som beskriver hela stadens dynamik? Hur kan dessa mycket olika tolkningar av ordet landskap existera under en och samma paroll – Landscape Urbanism? Denna uppsats behandlar dessa olika tolkningar, men presenterar även ett sätt att hantera detta till synes alldagliga men mångfacetterade ord. Due to Landscape Urbanism the term landscape has experienced a recent hausse within architecture and urban design discourse. With this new attention directed towards the landscape a new need has emerged: to discuss what is meant with this multivalent word. With this in focus, this thesis deals with the complications that occur when the word landscape and its oftentimes contradictory meanings are used without communicating what is meant. In accordance to linguistic theories I argue that language and hence semantics, the meaning of words, is of great importance when formulating and creating new urban theories such as Landscape Urbanism. What is really meant with Landscape in Landscape Urbanism? How come the term refers to surface conditions between buildings, but is also used to describe the dynamics of the whole city? How can these two very different interpretations of the term exist under one formulation – Landscape Urbanism? This thesis deals with these differing semantics, but also presents a way to handle this apparently ordinary, but multi-faceted word

Central Peripheries: speculation and strategy for a land less mentioned

As the contemporary discourse surrounding urbanism is almost exclusively focusing on aspects of density and traditional urban qualities, it entrenches notions of what constitutes a proper city and countryside. But beyond this urban-rural dichotomy is another highly contemporary landscape. A territory usually mentioned as sprawl, peri-urban, wasteland, edge city, etc. Although its existence is due to mobilization, telecommunications, globalization and other phenomena of modern life, it is a landscape without an own name or place in public awareness. This thesis provides a case study of how to map and intervene in such a landscape, specifically along the border between Malmö and Burlöv municipalities in southern Sweden. Its structure is composed of a sequence of three parts: 1 Spatial Conditions: Divided up in the sections Network, Fringe and Void. These describe and discuss the dynamics between technology, economics, social practices and planning in a landscape that is neither urban nor rural. 2 Spatial Investigations: In which the creative agency of mapping is used to produce maps that reveal the complexity of the landscape between Malmö and Burlöv. As the municipal border comprises two administrative peripheries it is chosen as a section through this ambiguous landscape. 3 Spatial Interventions: A proposal for design strategy that aims to provide a platform for a new awareness and appropriation of the peri-urban landscape. The strategy consists of five parts spanning from basic infrastructures to modular furniture and is combined with a concept for gamifying the site to create incentives for its use. The thesis is concluded with a discussion of the possible effects of an eventual implementation of the design strategy, as well as a reflection on why landscape architects should take the role as active agents in peri-urban landscapes.Då den samtida diskussionen rörande urbanism nästan uteslutande fokuserar på densitet och traditionell stadsmässighet cementeras föreställningar om vad som utgör stad respektive landsbygd. Men bortom den urban-rurala dikotomin finns ett annat, högst samtida, landskap. Detta territorium omnämns ofta som sprawl, peri-urbant, skräpmarker, stadsrand, etc. Trots att dess existens beror på mobilitet, telekommunikation, globalisering och andra typiskt moderna fenomen, saknar detta landskap ett eget namn och plats i det offentligas medvetenhet. Detta examensarbete utgör en fallstudie i hur man karterar och ingriper i ett sådant landskap, specifikt längs gränsen mellan Malmö och Burlöv kommuner i södra Sverige. Arbetets struktur är uppdelat i en sekvens av tre delar: 1 Rumsliga tillstånd: Utgörs av delarna Nätverk, Rand och Tomrum. Dessa beskriver och diskuterar dynamiken mellan teknologi, ekonomi, sociala handlingar och planering i ett landskap som varken är urbant eller ruralt. 2 Rumsliga undersökningar: I vilket karteringens kreativa aspekt används för att producera kartor som avslöjar komplexiteten i landskapet mellan Malmö och Burlöv. Eftersom kommungränsen är sammansatt av två administrativa periferier används denna som en sektionslinje genom detta mångtydiga landskap. 3 Rumsliga ingrepp: Ett förslag till designstrategi som ämnar utgöra en plattform för en ny medvetenhet och appropriering av det peri-urbana landskapet. Strategin utgörs av fem delar som spänner från grundläggande infrastrukturer till modulära möbler och är kombinerad med ett koncept för hur platsen kan spelifieras för att skapa incitament för dess användning. Examensarbetet avslutas med en diskussion rörande möjliga effekter av en eventuell implementering av designstrategin, samt en reflektion över varför landskapsarkitekter bör axla en aktiv roll i det peri-urbana landskapet