Developing Iodoarene Derivatives for Useful Oxidative Transformations and Biodegradable X-ray Materials

This thesis discloses two distinct applications of synthesized iodoarene-containing compounds: as hypervalent iodine (HI) organocatalysts and as biodegradable X-ray contrasting agents. This thesis also details a short chapter regarding the synthesis of rarely accessible chemical moieties: diazacyclobutenes and 2-imidothioimidates. Recently, organohypervalent iodine compounds have prevailed as valuable synthetic reagents. These reagents have the ability to efficiently perform transition metal-like transformations while possessing environmentally friendly properties. However, a persistent obstacle in utilizing hypervalent iodine (HI) reagents has been promoting synthetic reactions with high reactivities and enantioselectivities. To this fact, it is necessary to further improve upon the field of hypervalent iodine chemistry, especially in the context of the development of new, modular, and tunable catalyst scaffolds. The first chapter of this thesis reviews the background and history of hypervalent iodine compounds. The second chapter describes the progress that has been made in the field of catalysis, with emphasis on asymmetric organocatalysis. The third chapter details the advances that were made to design, develop, and understand the reactivity of iodoarene-containing catalysts in hypervalent iodine(III)-mediated transformations. Furthermore, the third chapter provides insight on merging the fields of hypervalent iodine chemistry with organocatalysis and asymmetric synthesis to generate chiral catalysts that can be used in valuable organic transformations. These organocatalysts have the potential to be broadly applicable and to impact synthetically useful transformations by imparting high yields and stereoselectivities. Synthetic materials have proven to have a key role in the medical field. In particular, polymeric materials have exhibited significance as contrast imaging agents due to their inherent biodegradable and biocompatible profile. The fourth chapter of this thesis describes the efficient synthesis, characterization, and X-ray evaluation of several iodoarene-containing polyesters. Synthetic chemists are continuously searching for novel and efficient bond-forming methods to produce new chemical species. The final chapter of this thesis describes a new strategy to generate unique chemical motifs (diazacyclobutenes and 2-imidothioimidates) via a formal [2+2] cycloaddition between electron rich alkynes and azodicarbonyl reagents

Assessing the impact of health technology assessment in the Netherlands

Copyright © Cambridge University Press 2008Objectives: Investments in health research should lead to improvements in health and health care. This is also the remit of the main HTA program in the Netherlands. The aims of this study were to assess whether the results of this program have led to such improvements and to analyze how best to assess the impact from health research.Methods: We assessed the impact of individual HTA projects by adapting the "payback framework" developed in the United Kingdom. We conducted dossier reviews and sent a survey to principal investigators of forty-three projects awarded between 2000 and 2003. We then provided an overview of documented output and outcome that was assessed by ten HTA experts using a scoring method. Finally, we conducted five case studies using information from additional dossier review and semistructured key informant interviews.Results: The findings confirm that the payback framework is a useful approach to assess the impact of HTA projects. We identified over 101 peer reviewed papers, more than twenty-five PhDs, citations of research in guidelines (six projects), and implementation of new treatment strategies (eleven projects). The case studies provided greater depth and understanding about the levels of impact that arise and why and how they have been achieved.Conclusions: It is generally too early to determine whether the HTA program led to actual changes in healthcare policy and practice. However, the results can be used as a baseline measurement for future evaluation and can help funding organizations or HTA agencies consider how to assess impact, possibly routinely. This, in turn, could help inform research strategies and justify expenditure for health research.This research is funded by ZonMw, the Netherlands organization for health research and development (project 945-15-001)

Fecundity and longevity of roaming dogs in Jaipur, India

<p>Abstract</p> <p>Background</p> <p>Estimates of demographic parameters, such as age-specific survival and fecundity, age at first pregnancy and litter size, are required for roaming dogs (i.e. dogs that are neither confined nor restricted) to assess the likely effect of proposed methods of population control. Data resulting from individual identification of dogs spayed as part of an Animal Birth Control (ABC) programme in Jaipur, India, are used to derive such parameters for the roaming dog population of that city.</p> <p>Results</p> <p>The percentage of females becoming pregnant in any given year was estimated by inspection of over 25,000 females caught for spaying from 1995 to 2006. The point estimate is 47.5% with a 95% confidence interval from 44% to 51%. Adult annual survival of spayed females was estimated by recapture of 62 spayed females from 2002 to 2006. The point estimate is 0.70 (95% confidence interval from 0.62 to 0.78), corresponding to an expected total lifespan of 3.8 years for a spayed female at one year old.</p> <p>Conclusion</p> <p>Recording the pregnancy status of dogs collected for spaying and individual marking of dogs released following spaying can provide estimates of some of the demographic parameters essential for predicting the future effectiveness of an ABC programme. Further, we suggest that recording the number and location of spayed and unspayed dogs encountered by the catching teams could be the most effective way to monitor the size and composition of the roaming dog population.</p

Efficient Circulation of Railway Rolling Stock

Railway rolling stock (locomotives, carriages, and train units) is one of the most significant cost sources for operatorsof passenger trains, both public and private. Rolling stock costsare due to material acquisition, power supply, and material maintenance. The efficient circulation of rolling stock material is therefore one of the objectives pursued. In this paper we focus on the circulation of train units on a single line. In order to utilize the train units on this line in an efficient way, they are added to or removed from the trains in certain stations, according to the passengers

Next-generation metrics: responsible metrics and evaluation for open science

This is the final report of the European Commission's Expert Group on Altmetrics, which undertook its work over the course of 2016. The report outlines a framework for next-generation metrics in the context of the EC's Open Science agenda and includes a series of recommendations for how responsible metrics can be built into the design and evaluation of the EU's Ninth Framework Programme (FP9)

Owl and Lizard: Patterns of Head Pose and Eye Pose in Driver Gaze Classification

Accurate, robust, inexpensive gaze tracking in the car can help keep a driver safe by facilitating the more effective study of how to improve (1) vehicle interfaces and (2) the design of future Advanced Driver Assistance Systems. In this paper, we estimate head pose and eye pose from monocular video using methods developed extensively in prior work and ask two new interesting questions. First, how much better can we classify driver gaze using head and eye pose versus just using head pose? Second, are there individual-specific gaze strategies that strongly correlate with how much gaze classification improves with the addition of eye pose information? We answer these questions by evaluating data drawn from an on-road study of 40 drivers. The main insight of the paper is conveyed through the analogy of an "owl" and "lizard" which describes the degree to which the eyes and the head move when shifting gaze. When the head moves a lot ("owl"), not much classification improvement is attained by estimating eye pose on top of head pose. On the other hand, when the head stays still and only the eyes move ("lizard"), classification accuracy increases significantly from adding in eye pose. We characterize how that accuracy varies between people, gaze strategies, and gaze regions.Comment: Accepted for Publication in IET Computer Vision. arXiv admin note: text overlap with arXiv:1507.0476

Negative symptoms predict high relapse rates and both predict less favorable functional outcome in first episode psychosis, independent of treatment strategy

BACKGROUND: In first episode psychosis (FEP) baseline negative symptoms (BNS) and relapse both predict less favorable functional outcome. Relapse-prevention is one of the most important goals of treatment. Apart from discontinuation of antipsychotics, natural causes of relapse are unexplained. We hypothesized that BNS, apart from predicting worse functional outcome, might also increase relapse risk. METHODS: We performed a post-hoc analysis of 7-year follow-up data of a FEP cohort (n = 103) involved in a dose-reduction/discontinuation (DR) vs. maintenance treatment (MT) trial. We examined: 1) what predicted relapse, 2) what predicted functional outcome, and 3) if BNS predicted relapse, whether MT reduced relapse rates compared to DR. After remission patients were randomly assigned to DR or MT for 18 months. Thereafter, treatment was uncontrolled. OUTCOMES: BNS and duration of untreated psychosis (DUP) predicted relapse. Number of relapses, BNS, and treatment strategy predicted functional outcome. BNS was the strongest predictor of relapse, while number of relapses was the strongest predictor of functional outcome above BNS and treatment strategy. Overall and within MT, but not within DR, more severe BNS predicted significantly higher relapse rates. Treatment strategies did not make a difference in relapse rates, regardless of BNS severity. INTERPRETATION: BNS not only predicted worse functional outcome, but also relapses during follow-up. Since current low dose maintenance treatment strategies did not prevent relapse proneness in patients with more severe BNS, resources should be deployed to find optimal treatment strategies for this particular group of patients

Reprint of:Negative symptoms predict high relapse rates and both predict less favorable functional outcome in first episode psychosis, independent of treatment strategy

Background: In first episode psychosis (FEP) baseline negative symptoms (BNS) and relapse both predict less favorable functional outcome. Relapse-prevention is one of the most important goals of treatment. Apart from discontinuation of antipsychotics, natural causes of relapse are unexplained. We hypothesized that BNS, apart from predicting worse functional outcome, might also increase relapse risk. Methods: We performed a post-hoc analysis of 7-year follow-up data of a FEP cohort (n = 103) involved in a dose-reduction/discontinuation (DR) vs. maintenance treatment (MT) trial. We examined: 1) what predicted relapse, 2) what predicted functional outcome, and 3) if BNS predicted relapse, whether MT reduced relapse rates compared to DR. After remission patients were randomly assigned to DR or MT for 18 months. Thereafter, treatment was uncontrolled. Outcomes: BNS and duration of untreated psychosis (DUP) predicted relapse. Number of relapses, BNS, and treatment strategy predicted functional outcome. BNS was the strongest predictor of relapse, while number of relapses was the strongest predictor of functional outcome above BNS and treatment strategy. Overall and within MT, but not within DR, more severe BNS predicted significantly higher relapse rates. Treatment strategies did not make a difference in relapse rates, regardless of BNS severity. Interpretation: BNS not only predicted worse functional outcome, but also relapses during follow-up. Since current low dose maintenance treatment strategies did not prevent relapse proneness in patients with more severe BNS, resources should be deployed to find optimal treatment strategies for this particular group of patients. (C) 2019 Elsevier B.V. All rights reserved