Developing clinical prediction models for diabetes classification and progression

Patients with type 1 and type 2 diabetes have very different treatment and care requirements. Overlapping phenotypes and lack of clear classification guidelines make it difficult for clinicians to differentiate between type 1 and type 2 diabetes at diagnosis. The rate of glycaemic deterioration is highly variable in patients with type 2 diabetes but there is no single test to accurately identify which patients will progress rapidly to requiring insulin therapy. Incorrect treatment and care decisions in diabetes can have life-threatening consequences. The aim of this thesis is to develop clinical prediction models that can be incorporated into routine clinical practice to assist clinicians with the classification and care of patient diagnosed with diabetes. We addressed the problem first by integrating features previously associated with classification of type 1 and type 2 diabetes to develop a diagnostic model using logistic regression to identify, at diagnosis, patients with type 1 diabetes. The high performance achieved by this model was comparable to that of machine learning algorithms. In patients diagnosed with type 2 diabetes, we found that patients who were GADA positive and had genetic susceptibility to type 1 diabetes progressed more rapidly to requiring insulin therapy. We built upon this finding to develop a prognostic model integrating predictive features of glycaemic deterioration to predict early insulin requirement in adults diagnosed with type 2 diabetes. The three main findings of this thesis have the potential to change the way that patients with diabetes are managed in clinical practice. Use of the diagnostic model developed to identify patients with type 1 diabetes has the potential to reduce misclassification. Classifying patients according to the model has the benefit of being more akin to the treatment needs of the patient rather than the aetiopathological definitions used in current clinical guidelines. The design of the model lends itself to implementing a triage-based approach to diabetes subtype diagnosis. Our second main finding alters the clinical implications of a positive GADA test in patients diagnosed with type 2 diabetes. For identifying patients likely to progress rapidly to insulin, genetic testing is only beneficial in patients who test positive for GADA. In clinical practice, a two-step screening process could be implemented - only patients who test positive for GADA in the first step would go on for genetic testing. The prognostic model can be used in clinical practice to predict a patient’s rate of glycaemic deterioration leading to a requirement for insulin. The availability of this data will enable clinical practices to more effectively manage their patient lists, prioritising more intensive follow up for those patients who are at high risk of rapid progression. Patients are likely to benefit from tailored treatment. Another key clinical use of the prognostic model is the identification of patients who would benefit most from GADA testing saving both inconvenience to the patient and a cost-benefit to the health service

Revisiting Settlement Contemporaneity and Exploring Stability and Instability: Case Studies from the Indus Civilization.

"Map overestimation," or "the contemporaneity problem," derives from the assumption that settlements identified during surface surveys were occupied throughout individual periods. Inductive and simulation analysis have been used to ascertain the degree of contemporaneity in surface survey data sets, as variation in settlement location is critical for understanding population density and demography, which inform social, economic and political interpretations. This paper revisits the inductive approach to interrogating survey data developed by W. M. Sumner and the simulation model approach developed by R. E. Dewar to explore the survey data from two regions within South Asia's Indus civilization. This analysis demonstrates the strengths and weaknesses of these approaches. It also highlights the variability in settlement systems in different areas within the Indus civilization and shows that consideration of stability and instability within settlement systems is an important factor when considering dynamics of resilience and sustainability.ER

The Properties of Brightest Cluster Galaxies in X-Ray Selected Clusters

We present the K-band Hubble diagram for 162 brightest cluster galaxies (BCGs) in X-ray selected clusters, 0.01<z<0.83. The sample incorporates that of Burke, Collins, & Mann (2000) and includes additional infrared data from the 2MASS extended source catalogue. We show that below z=0.1 the BCGs show no correlation with their environment, however, above z=0.1 BCGs in more X-ray luminous clusters are more uniform in their photometric properties. This suggests that there may be two populations of BCGs which have different evolutionary histories.Comment: 2 pages, to appear in the proceedings of the Sesto 2001 conference on tracing cosmic evolution with galaxy cluster

Using consensus analysis to assess mental models about water use and management in the Crocodile River catchment, South Africa

The content, structure, and distribution of mental models can be elicited and measured using a variety of methods. In this article we explore a method for eliciting mental models within the context of water use and management in South Africa. This method is consensus analysis, a technique developed in cognitive anthropology. We used it to analyze qualitative data from semistructured interviews, pilesorts, and questionnaires to test quantitatively the degree of sharing and diversity of mental models within and across social groups. The consensus analysis method focused on comparing the mental models of two key stakeholder groups in the Crocodile River catchment in South Africa, i.e., conservationists and irrigators, to better understand the level of consensus between these groups. We specifically investigated the level of agreement regarding: (1) major water users of the Crocodile River, (2) causes of the current problems with flows in the river, (3) consequences of the river not flowing, and 4) priorities for future use. We discuss the results and examine the strengths and challenges of consensus analysis for eliciting and measuring mental models. We also evaluated the usefulness of this method in assisting natural resource managers to identify strategies for improving integrated management of water resources

Quantitative criteria for choosing targets and indicators for sustainable use of ecosystems

The authors thank Simon Greenstreet, Cristina Herbon, Simon Jennings, Tiziana Luisetti, Lucille Paltriguera, and Christian Wilson for comments on previous versions of this paper. This work has resulted from the DEVOTES (DEVelopment Of innovative Tools for understanding marine biodiversity and assessing Good Environmental Status) project funded by the EU under the 7th Framework Programme, ‘The Ocean of Tomorrow’ Theme (No. 308392), www.devotes-project.eu. Further, A.G.R. was partially funded by the Natural Environment Research Council and the UK Department for Food, Environment and Rural Affairs (Defra) within the Marine Ecosystems Research Program (MERP), C.P.L. by Defra (M1228), A.Z. by BIOsingle bondC3 within the joint Baltic Sea Research and Development Programme (EU 7th and Research Council of Lithuania, BONUS-1/2014), and M.C.U. by the Spanish Programme for talent and employability in I + D + i ‘Torres Quevedo’

Characterizing the degradation of alginate hydrogel for use in multilumen scaffolds for spinal cord repair

Alginate was studied as a degradable nerve guidance scaffold material in vitro and in vivo. In vitro degradation rates were determined using rheology to measure the change in shear modulus vs time. The shear modulus decreased from 155 kPa to 5 kPa within 2 days; however, alginate samples maintained their superficial geometry for over 28 days. The degradation behavior was supported by materials characterization data showing alginate consisted of high internal surface area (400 m2/g), which likely facilitated the release of cross‐linking cations resulting in the rapid decrease in shear modulus. To assess the degradation rate in vivo, multilumen scaffolds were fabricated using a fiber templating technique. The scaffolds were implanted in a 2‐mm‐long T3 full transection rodent spinal cord lesion model for 14 days. Although there was some evidence of axon guidance, in general, alginate scaffolds degraded before axons could grow over the 2‐mm‐long lesion. Enabling alginate‐based scaffolds for nerve repair will likely require approaches to slow its degradation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 611–619, 2016.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137597/1/jbma35600.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137597/2/jbma35600_am.pd

Cross-Lagged Relations Between Motives and Substance Use: Can Use Strengthen Your Motivation Over Time?

Motives for substance use have garnered considerable attention due to the strong predictive utility of this construct, both in terms of use and problems associated with use. The current study examined the cross-lagged relations between alcohol use and motives, and marijuana use and motives over three yearly assessment periods in a large sample (N = 526, 48% male) of college students. The relations between substance use and motives were assessed at each time point, allowing for the examination of these inter-relations over time. Results indicated different trends based on the type of substance. For alcohol use, cross-lagged trends were found between freshman and sophomore year for coping, social, and conformity motives with cross-lagged relations between enhancement motives and alcohol use across all years. However, outside of enhancement motives, cross-lagged relations were not found between sophomore and junior year. In contrast, cross-lagged effects were found for marijuana use and coping, enhancement, and expansion motives between sophomore and junior year, but not freshman year. These results suggest that people’s expectations that drinking or smoking marijuana makes activities more reinforcing and helps them cope with distress may perpetuate use. In turn, use itself may enhance these expectations over time. Results have direct implications for treatment, with recommended focus on motives, behavior activation, and healthy coping skills in order to interrupt the cycle of substance use

Road induced edge effects on a forest bird community in tropical Asia

Background: Edge effects cause changes in bird community richness, abundance, and/or distribution within a landscape, but the avian guilds most influenced can vary among regions. Although Southeast Asia has the highest rates of deforestation and projected species loss, and is currently undergoing an explosive growth in road infrastructure, there have been few studies of the effects of forest edges on avian communities in this region. Methods: We examined avian community structure in a dry evergreen forest in northeastern Thailand adjacent to a five-lane highway. We evaluated the richness and abundance of birds in 11 guilds at 24 survey points on three parallel transects perpendicular to the edge. At each point, 10-min surveys were conducted during February‒August 2014 and March‒August 2015. Vegetation measurements were conducted at 16 of the bird survey points and ambient noise was measured at all 24 survey points. Results: We found a strongly negative response to the forest edge for bark-gleaning, sallying, terrestrial, and understory insectivores and a weakly negative response for arboreal frugivore-insectivores, foliage gleaning insectivores, and raptors. Densities of trees and the percentage canopy cover were higher in the interior, and the ambient noise was lower. In contrast, arboreal nectarivore-insectivores responded positively to the forest edge, where there was a higher vegetation cover in the ground layer, a lower tree density, and a higher level of ambient noise. Conclusion: Planners should avoid road development in forests of high conservation value to reduce impacts on biodiversity. Where avoidance is impossible, a number of potential mitigation methods are available, but more detailed assessments of these are needed before they are applied in this region

Late childhood interpersonal callousness and conduct problem trajectories interact to predict adult psychopathy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135659/1/jcpp12598_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135659/2/jcpp12598.pd