Bayesian methods for the design and analysis of complex follow-up studies

My doctoral research focused on two topics: i) models for the analysis of multi-state time-to-event data; and ii) decision-theoretic approaches for the design of clinical trials with a survival endpoint. For the first, I developed stochastic processes useful for the Bayesian non-parametric analysis of follow-up studies where patients may experience multiple events relevant to their prognosis. For the second, I developed an approach that uses data from early clinical trials to specify the statistical test used in a confirmatory survival study, accounting for the possible failure of standard assumptions. In this thesis, I describe 3 research papers that report my contributions. Part of my work has been conducted while a visiting researcher at the Dana-Farber Cancer Institute, Boston, Massachusetts (United States of America)

Quilatador de oro, plata y piedras

Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2009-2010Sign.: [parágrafo]8, A-Z8, 2A-2B8, 2C4Port. con grab. xil., retr. del autorGrab. xil. intercalados en el text

Título: Segundo tratado de los reloxes solares

Port. con grab. xil., representando al autor.Texto con apostillas marginales.Il. son xil., algunas a toda plana.Copia digital : Junta de Castilla y León. Consejería de Cultura y Turismo, 2014Sign.: []2, A-2A6, 2B4, 2C1

The association of the original OSHA chemical hazard communication standard with reductions in acute work injuries/illnesses in private industry and the industrial releases of chemical carcinogens

Background OSHA predicted the original chemical Hazard Communication Standard (HCS) would cumulatively reduce the lost workday acute injury/illness rate for exposure events by 20% over 20 years and reduce exposure to chemical carcinogens. Methods JoinPoint trend software identified changes in the rate of change of BLS rates for days away from work for acute injuries/illnesses during 1992–2009 for manufacturing and nonmanufacturing industries for both chemical, noxious or allergenic injury exposure events and All other exposure events. The annual percent change in the rates was used to adjust observed numbers of cases to estimate their association with the standard. A case‐control study of EPA's Toxic Release Inventory 1988–2009 data compared carcinogen and non‐carcinogens' releases. Results The study estimates that the HCS was associated with a reduction in the number of acute injuries/illnesses due to chemical injury exposure events over the background rate in the range 107,569–459,395 (Hudson method/modified BIC model) depending on whether the HCS is treated as a marginal or sole factor in the decrease. Carcinogen releases have declined at a substantially faster rate than control non‐carcinogens. Discussion The previous HCS standard was associated with significant reductions in chemical event acute injuries/illnesses and chemical carcinogen exposures. Am. J. Ind. Med. 57:138–152, 2014. © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102719/1/ajim22269.pd

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

The cognitive effects of computational thinking: A systematic review and meta-analytic study

In this paper, we review and meta-analyze the findings of experimental studies published between 2006 and 2022 that examined the effects of coding and programming interventions on children's core and higher order executive functions (response inhibition, working memory, cognitive flexibility, planning and problem solving). The systematic review and meta-analysis aimed to address three research questions: 1) Which executive functions are most impacted by the teaching of CT? 2) Which instructional modality (educational robotics/virtual coding/unplugged coding) is most effective in enhancing executive function skills in learners aged 4–16 years? and 3) Does the cognitive effectiveness of coding vary with children's age? A total of 19 studies with 1523 participants met the selection criteria for the systematic review. The meta-analysis included 11 of those studies. The results reveal beneficial effects of structured virtual and tangible coding (educational robotics) activities for preschoolers and first graders, and significant effects of more unstructured virtual coding activities (e.g., Scratch-based) for older students. A multivariate fixed-effects model meta-analysis shows that the teaching of coding significantly improves problem-solving with the highest effect (dppc2 = 0.89), but also planning (dppc2 = 0.36), and inhibition and working memory with lower effects (dppc2 = 0.17, dppc2 = 0.20)

Faculty and Student Online Mentoring Preferences

Isolation of online doctoral students intensifies when they transition from coursework to the dissertation/capstone phase, limiting them to interacting with their mentors. A three-round modified Delphi study was conducted to examine mentoring preferences of online doctoral students and faculty. The first round provided qualitative data regarding the preferred mentoring practices for faculty and alumni. Round 1 qualitative data were organized into Likert questions and used in the second round, which resulted in data about frequency of mentoring practices for the same participants from Round 1. The third round provided data about importance of each preference rated by faculty and current students. Findings indicated a dichotomy was present in that mentees’ academic self-esteem appeared to be tied to faculty being responsive. Faculty emphasized mentee autonomy while mentees wanted frequent contact with faculty

Manual para construir toda especie de relojes de sol

Ilustrado con 28 grabados intercalados en el texto para su mayor comprensiónCopia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2009-201