Why Transportation Mega-Projects (Often) Fail? Case Studies of Selected Transportation Mega-Projects in the New York City Metropolitan Area

This thesis explores the reasons why so few transportation mega-projects have been successfully implemented for nearly half a century in the New York City metropolitan area. Case studies of several major transportation projects are presented and analyzed. Interviews with project managers and other transportation professionals responsible for implementing mega-projects provided insight into some of the challenges faced by practitioners. This thesis suggests changes in project delivery methods and funding mechanisms that may help improve implementation of large, complex transportation projects that have a potential of providing significant public benefits. But, ultimately, fundamental institutional changes may be needed in order to effect meaningful improvements in mega-project delivery success rates and the type of mega-projects implemented. A key underlying planning/political economy issue is how to support the economic vitality of central cities in the face of an aging transportation system infrastructure and increasing competition for scarce funding resources while providing adequate protection of civil society and the environment

"You Have to Have a Relationship First": Student-teacher Relationships as a Focus of School Reform.

While conducting fieldwork in two “alternative” high schools, I was struck by how consistently the educators I interviewed invoked “relationships” with young people as the key to engaging them in school. Their emphasis on the primacy of student-teacher relationships echoes across a varied body of academic research literature. This dissertation synthesizes an instructive sample of that literature into a symposium, or philosophical conversation, exploring the many meanings, ramifications, and empirical bases of the idea of prioritizing student-teacher relationships as a focus of school reform. The conversation unfolds in three parts. Chapter 1 specifies five different assertions about why and how student-teacher relationships matter, drawing on a range of perspectives including (among others) Attachment Theory, social-constructivist theories of learning, Culturally Relevant Pedagogy, Self-Determination Theory, Carl Rogers’s theory of “learner-centered” education, and Nel Noddings’s ethic of caring. Although different ways of framing the value of student-teacher relationships are not necessarily mutually exclusive, disentangling them helps us critically examine the distinctive premises, problems, and possibilities that each one brings to the fore. Chapter 2 considers three families of strategies for fostering better student-teacher relationships through changes to the institutional environment. In particular, I discuss strategies for building protected time for relationship-building into the school schedule, for designing accountability structures that rely less on standardization, and for creating university-based teacher education programs that embody an ethos of care. Chapter 3 offers close readings of leading examples of empirical studies related to student-teacher relationships, representing diverse methodological approaches including experimental design, statistical modeling, meta-analysis, case study, and narrative. Drawing especially on the work of Bent Flyvbjerg, I suggest that the “usefulness” of research lies not only in the validity of the findings it reports or the theory it generates, but in the opportunity it affords readers to develop their own impressions, explanations, and plans as they engage with the text. This dissertation is itself an attempt at scholarship that aims to stimulate active questioning and personal reflection. Thus, it ends not with any “conclusions,” but with a series of provocations intended to extend the conversation.PHDEducational StudiesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/135849/1/jeremygt_1.pd

Continuous Nucleation and Size Dependent Growth Kinetics of Indium Phosphide Nanocrystals

Aminophosphines derived from N,N′-disubstituted ethylenediamines (R–N(H)CH2CH2N(H)–R; R = ortho-tolyl, phenyl, benzyl, iso-propyl, and n-octyl) were used to adjust the kinetics of InP nanocrystal formation by more than 1 order of magnitude. Ultraviolet–visible absorption and 31P nuclear magnetic resonance measurements demonstrate that the rate of nanocrystal formation is limited by the precursor reactivity. At low temperature (180 °C), crystal nucleation is concurrent with growth throughout the reaction, rather than occurring in a burst at early times. The low temperature produces a narrow range of small sizes (d = 4.2–4.9 nm) regardless of the precursor used. Higher temperatures (up to 270 °C) promote growth to larger sizes (d ≤ 7.8 nm), shorten the nucleation period, and create conditions where the final size is controlled by the precursor conversion reactivity. The temperature dependence is proposed to arise from growth kinetics that slow as the nanocrystal size increases, a novel surface attachment limited size distribution-focusing mechanism. Such a mechanism supports a narrow size distribution without separating the nucleation and growth phases

Prostate-specific membrane antigen expression in the vasculature of primary lung carcinomas associates with faster metastatic dissemination to the brain

Glioblastomas and brain metastases (BM) of solid tumours are the most common central nervous system neoplasms associated with very unfavourable prognosis. In this study, we report the association of prostate-specific membrane antigen (PSMA) with various clinical parameters in a large cohort of primary and secondary brain tumours. A tissue microarray containing 371 cases of ascending grades of gliomas pertaining to astrocytic origin and samples of 52 cases of primary lung carcinomas with matching BM with follow-up time accounting to 10.4 years was evaluated for PSMA expression using immunohistochemistry. In addition, PSMA expression was studied in BM arising from melanomas and breast carcinomas. Neovascular expression of PSMA was evident alongside with high expression in the proliferating microvasculature of glioblastomas when compared to the tumour cell expression. This result correlated with the results obtained from the in silico (cancer genome databases) analyses. In gliomas, only the vascular expression of PSMA associated with poor overall survival but not the tumour cell expression. In the matched primary lung cancers and their BM (n = 52), vascular PSMA expression in primary tumours associated with significantly accelerated metastatic dissemination to the brain with a tendency towards poor overall survival. Taken together, we report that the vascular expression of PSMA in the primary and secondary brain tumours globally associates with the malignant progression and poor outcome of the patients.Peer reviewe

A systematic review of qualitative studies of adults' experiences of being assessed for psychological therapies

Objective To synthesize the qualitative literature on adults’ experiences of psychological therapy assessments. The review was led by people with experience of undergoing assessments, with high levels of client involvement throughout. Search strategy A comprehensive search of electronic databases was undertaken, with additional search strategies employed to locate further literature. Inclusion criteria Studies were included that qualitatively explored the experiences of people aged 16+ who had been assessed for psychological therapy services. Assessments could be structured or unstructured. Qualitative was defined as any analysed account of people's experiences, including qualitative survey data. Data extraction and synthesis Literature quality was appraised using the Critical Appraisal Skills Program checklist, modified to include client involvement and intersectionalities. Following data extraction, thematic synthesis was used to synthesize findings across studies. Results Of 12 743 titles were screened, with 13 studies relevant to the review. Themes and subthemes were identified at three stages of the assessment process: the journey to the assessment, at the assessment, and after the assessment. Findings highlighted the emotional impact of assessments, collaboration, intersectionalities, rights, pathologization, socioeconomic restrictions, and information and support needs. Implications and limitations were indicated. Discussion and conclusions Findings were situated within the trauma‐informed (TIA) literature. Trauma‐informed assessment principles, including collaborative assessments, may be fruitful means of improving people's experiences. Whilst the benefits of collaboration appear self‐evident, explicitly collaborative approaches were not the norm, nor were studies conducted independently. Further service user research is needed. A greater understanding of the experience of minority groups is also needed

Immune checkpoint blockade – how does it work in brain metastases?

Immune checkpoints restrain the immune system following its activation and their inhibition unleashes anti-tumor immune responses. Immune checkpoint inhibitors revolutionized the treatment of several cancer types, including melanoma, and immune checkpoint blockade with anti-PD-1 and anti-CTLA-4 antibodies is becoming a frontline therapy in metastatic melanoma. Notably, up to 60% of metastatic melanoma patients develop metastases in the brain. Brain metastases (BrM) are also very common in patients with lung and breast cancer, and occur in ∼20–40% of patients across different cancer types. Metastases in the brain are associated with poor prognosis due to the lack of efficient therapies. In the past, patients with BrM used to be excluded from immune-based clinical trials due to the assumption that such therapies may not work in the context of “immune-specialized” environment in the brain, or may cause harm. However, recent trials in patients with BrM demonstrated safety and intracranial activity of anti-PD-1 and anti-CTLA-4 therapy. We here discuss how immune checkpoint therapy works in BrM, with focus on T cells and the cross-talk between BrM, the immune system, and tumors growing outside the brain. We discuss major open questions in our understanding of what is required for an effective immune checkpoint inhibitor therapy in BrM

Modelling the neuropathology of lysosomal storage disorders through disease-specific human induced pluripotent stem cells

Mucopolysaccharidosis II (MPS II) is a lysosomal storage disorder (LSD), caused by iduronate 2-sulphatase (IDS) enzyme dysfunction. The neuropathology of the disease is not well understood, although the neural symptoms are currently incurable. MPS II-patient derived iPSC lines were established and differentiated to neuronal lineage. The disease phenotype was confirmed by IDS enzyme and glycosaminoglycan assay. MPS II neuronal precursor cells (NPCs) showed significantly decreased self-renewal capacity, while their cortical neuronal differentiation potential was not affected. Major structural alterations in the ER and Golgi complex, accumulation of storage vacuoles, and increased apoptosis were observed both at protein expression and ultrastructural level in the MPS II neuronal cells, which was more pronounced in GFAP + astrocytes, with increased LAMP2 expression but unchanged in their RAB7 compartment. Based on these finding we hypothesize that lysosomal membrane protein (LMP) carrier vesicles have an initiating role in the formation of storage vacuoles leading to impaired lysosomal function. In conclusion, a novel human MPS II disease model was established for the first time which recapitulates the in vitro neuropathology of the disorder, providing novel information on the disease mechanism which allows better understanding of further lysosomal storage disorders and facilitates drug testing and gene therapy approaches