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The PhD project focussed on the application of a cobalt tetraazamacrocyclic complex, in the literature commonly referred to as [Co(CR)Cl2]+ as a molecular catalyst for the hydrogen evolution reaction (HER). This was within the broader scope of the EU MSCA H2020 ITN ‘eSCALED’ project, which had as one of its central aims the objective to create an artificial leaf for the storage of solar energy in chemical fuels and, as part of this, sought the development of novel bio-inspired and scalable materials for the various components of the selected Polymer Electrolyte Membrane (PEM) electrolyser device architecture. This included researching molecular catalysts based on Earth-abundant first-row transition metals to replace the scarce noble metal-based materials currently used commercially in such technology.In this context, a number of projects were pursued: firstly, studies of the mechanism of the catalyst itself under organic electrocatalytic conditions were carried out, generating catalytic intermediates by controlled reduction and/or protonation of the catalyst and identifying them using spectroscopy (UV vis, NMR, EPR) and following the catalytic behaviour with electrochemical techniques. From this, an ECEC mechanism with a rate-determining second protonation step associated with the release of H2 was identified, noting in particular an initial protonation step on the macrocycle at the Co(II) state that was hypothesised to involve the macrocycle amine group acting as a proton relay under the investigated conditions.Secondly, a new synthetic strategy towards novel derivatives of [Co(CR)Cl2]+ modified at the para-position of the macrocycle pyridine group was developed, which enabled the synthesis of a pyrene-functionalised derivative which could be anchored onto sp2-carbon surfaces, such as multi-walled carbon nanotubes (MWCNTs), by -stacking interactions. The behaviour and catalytic properties of the immobilised catalyst were studied by electrochemical methods and compared with an analogous derivative functionalised at the macrocycle amine from collaborators at ICIQ, showing that both derivatives work as heterogenised electrocatalysts for the HER with high faradaic efficiencies and good stability over one hour at pH 2 and particularly pH 7, but the derivative functionalised on the pyridine displays higher current densities and greater stability, invoking some consideration of rational design principles for modifying molecular catalysts.Thirdly, studies of a photocatalytic system made up of copper indium sulfide quantum dots (CuInS2 QDs) as a photosensitiser with either [Co(CR)Cl2]+ or its benzoic acid-functionalised derivative were carried out in ascorbate buffer, focussing on the photocatalytic performance and electron transfer (ET) processes between the CuInS2 QDs and the catalyst to find explanations for the remarkable activity and robustness reported in literature for closely related systems. CuInS2 QDs modified to have a ‘hybrid-passivation’ ligand system making them suitable for immobilisation with NiO films were used, since this would be a requirement for future preparation of photoelectrodes with these materials. Photocatalytic hydrogen measurements, steady state fluorescence quenching, and ultrafast transient absorption spectroscopy indicated extremely rapid QD-catalyst ET processes for both the derivative and unmodified catalyst. To understand this behaviour, a static binding model with a strong binding equilibrium was adapted for the system. Considering the ability of QD particles to bind multiple catalyst molecules, the high efficiency of quenching followed a Poisson distribution up to about two equivalents of catalyst per QD. This prompts a reconsideration of the importance of anchoring groups for QD-catalyst ET efficiency in solution.Additionally, the development of printable MWCNT-based inks, immobilisation of catalysts on scalable printed electrodes and catalyst-functionalised conducting polymers were studied.; La thèse s’est concentrée sur l'application d'un complexe tétraazamacrocyclique de cobalt, nommé [Co(CR)Cl2]+ dans la littérature, comme catalyseur moléculaire pour la production d'hydrogène. Cette étude s’inscrit dans le cadre du projet EU MSCA H2020 ITN eSCALED, avec comme principal objectif la création d’une feuille artificielle pour stocker l'énergie solaire dans des combustibles chimiques. Les recherches entreprises visaient à développer de nouveaux matériaux bio-inspirés, adaptables et utilisables comme composant dans des électrolyseurs à membrane électrolytique polymère (PEM) : recherche de catalyseurs moléculaires basés sur des métaux de transition de la première série et abondants sur terre afin de remplacer les métaux rares et nobles actuellement utilisés dans ces technologies.Dans ce cadre, différents axes de recherche ont été investigués (entre autres) : premièrement, l’étude du mécanisme électrocatalytique du catalyseur a été réalisée en milieu organique, par génération d’intermédiaires catalytiques via réduction et/ou protonation contrôlée du catalyseur, en les caractérisant par des méthodes spectroscopiques (UV-vis, RMN, RPE) et en suivant le mécanisme réactionnel par des techniques électrochimiques. Un mécanisme de type ECEC a été identifié avec une seconde étape de protonation, associée à la libération de H2, qui détermine la la cinétique de réaction. La protonation initiale sur le macrocycle à l'état Co(II) implique que le groupe amine du macrocycle agit comme un relais de protons dans ces conditions.Deuxièmement, une nouvelle voie de synthèse de dérivés de [Co(CR)Cl2]+ modifiés en position para de la pyridine a été mise en place, permettant le greffage d’un groupement pyrène sur des surfaces de carbone de type sp2 sur des nanotubes de carbone multi-parois (MWCNTs) via des interactions d'empilement pi. Le comportement et les propriétés catalytiques du catalyseur ancré ont été étudiées par des méthodes électrochimiques et comparées à un dérivé analogue, modifié à une autre position, fourni par les collaborateurs à l'ICIQ. Nous avons démontré que les deux dérivés fonctionnent comme des électrocatalyseurs hétérogène dans la production d’hydrogène de manière stable avec des rendements faradiques élevés sur une heure à pH = 2 et notamment plus élevés à pH = 7. Cependant, le dérivé modifié sur la pyridine présente des densités de courant plus stables et plus élevées, ce qui concorde avec les principes de conception rationelle concernant la modification des catalyseurs moléculaires.Troisièmement, un système photocatalytique composé de boîtes quantiques de sulfure de cuivre-indium (QD CuInS2) a été étudié comme photosensibilisateur avec soit [Co(CR)Cl2]+ ou son dérivé modifié par un groupe acide benzoïque dans une solution tampon d'ascorbate. Nous avons étudié le processus photocatalytique, le transfert d'électrons (ET) entre les QD CuInS2 et le catalyseur, et les rendements associés. L’objectif étant d’expliquer l'activité et la robustesse remarquable rapportée pour les systèmes connexes. Des QD CuInS2avec un système de ligand pour la « passivation hybride » ont été préparés en raison de leur compatibilité avec les films NiO pour la préparation de photoélectrodes. Les mesures d'hydrogène photocatalytique, la fluorescence-trempe à l'état d'équilibre, et la spectroscopie d'absorption transitoire ultrarapide ont indiqué des processus ET extrêmement rapides entre les QD et les catalyseurs, quel que soit le catalyseur, modifié ou non. Afin de comprendre cette observation, une modélisation du système a été réalisée, impliquant une trempe statique très efficace. Compte tenu de la capacité des QD à lier plusieurs molécules de catalyseur, nous arrivons à une distribution suivant la loi de Poisson. Cela incite à reconsidérer la nécessité des groupes d'ancrage pour l'efficacité ET des QD pour les catalyseurs en solution.

The purpose of this systematic grounded theory study was to define and explain the development of homeschool teacher self-efficacy and its significance for homeschooling parents in Wisconsin. Bandura’s self-efficacy theory served as the initial theoretical framework for this study, as it defined four general sources of self-efficacy development: enactive mastery experiences, vicarious experiences through social models, social persuasion, and the regulation of physical and emotional states. Through surveys, open-ended interviews, focus groups, and artifacts received from 10 homeschooling parents, this study attempted to define how homeschooling parents perceive homeschool teacher self-efficacy, to what homeschooling parents attribute the development of homeschool teacher self-efficacy, and what homeschooling parents perceive are the benefits of homeschool teacher self-efficacy. As a result, a theory of homeschool teacher self-efficacy development and significance emerged from the research. This data-grounded theory postulates that homeschool teacher self-efficacy develops, operates, and benefits homeschooling parents through a four-stage agentic lifecycle model consisting of the initial stage, the transition stage, the stabilization and influence stage, and the outcomes stage.

A wireless wearable sensor on a paper substrate was used to continuously monitor respiratory behavior that can extract and deliver clinically relevant respiratory parameters to a smartphone. Intended to be placed horizontally at the midpoint of the costal margin and the xiphoid process as determined through anatomical analysis and experimental test, the wearable sensor is compact at only 40 × 35 × 6 mm

A wireless wearable sensor on a paper substrate was used to continuously monitor respiratory behavior that can extract and deliver clinically relevant respiratory parameters to a smartphone. Intended to be placed horizontally at the midpoint of the costal margin and the xiphoid process as determined through anatomical analysis and experimental test, the wearable sensor is compact at only 40 × 35 × 6 mm3 in size and 6.5 g weight including a 2.7 g lithium battery. The wearable sensor, consisting of an ultrasound emitter, an ultrasound receiver, wireless transmission system, and associated data acquisition, measures the linear change in circumference at the attachment location by recording and analyzing the changes in ultrasound pressure as the distance between the emitter and the receiver changes. Changes in ultrasound pressure corresponding to linear strain are converted to temporal lung volume data and are wirelessly transmitted to an associated custom-designed smartphone app. Processing the received data, the mobile app is able to display the temporal volume trace and the flow rate vs. volume loop graphs, which are standard plots used to analyze respiration. From the plots, the app is able to extract and display clinically relevant respiration parameters, including forced expiratory volume delivered in the first second of expiration (FEV1) and forced vital capacity (FVC). The sensor was evaluated with eight volunteers, showing a mean difference of the FEV1/FVC ratio as bounded by 0.00-4.25% when compared to the industry-standard spirometer results. By enabling continuous tracking of respiratory behavioral parameters, the wireless wearable sensor helps monitor the progression of chronic respiratory illnesses, including providing warnings to asthma patients and caregivers to pursue necessary medical assistance.

BackgroundUrinary tract infection (UTI) is a common childhood infection. Many febrile children require a urine sample to diagnose or exclude UTI. Collecting urine from young children can be time-consuming, unsuccessful or contaminated. Cost-effectiveness of each collection method in the emergency department is unknown.ObjectiveTo determine the cost-effectiveness of urine collection methods for precontinent children.MethodsA cost-effectiveness analysis was conducted comparing non-invasive (urine bag, clean catch and 5 min voiding stimulation for clean catch) and invasive (catheterisation and suprapubic aspirate (SPA)) collection methods, for children aged 0–24 months in the emergency department. Costs included equipment, staff time and hospital bed occupancy. If initial collection attempts were unsuccessful subsequent collection using catheterisation was assumed. The final outcome was a definitive sample incorporating progressive dipstick, culture and contamination results. Average costs and outcomes were calculated for initial collection attempts and obtaining a definitive sample. One-way and probabilistic sensitivity analyses were performed.ResultsFor initial collection attempts, catheterisation had the lowest cost per successful collection (GBP£25.98) compared with SPA (£37.80), voiding stimulation (£41.32), clean catch (£52.84) and urine bag (£92.60). For definitive collection, catheterisation had the lowest cost per definitive sample (£49.39) compared with SPA (£51.84), voiding stimulation (£52.25), clean catch (£64.82) and urine bag (£112.28). Time occupying a hospital bed was the most significant determinant of cost.ConclusionCatheterisation is the most cost-effective urine collection method, and voiding stimulation is the most cost-effective non-invasive method. Urine bags are the most expensive method. Although clinical factors influence choice of method, considering cost-effectiveness for this common procedure has potential for significant aggregate savings.

Purpose: Vincristine combined with camptothecin derivatives showed synergy in preclinical pediatric cancer models, and the combinations are effective in treatment of childhood solid tumors. We determined whether the synergy between vincristine and irinotecan extends to eribulin, another microtubule inhibitor. Experimental Design: Vincristine or eribulin, alone or combined with irinotecan, was studied in 12 xenograft models. Tumor regression and time to event were used to assess antitumor activity. Pharmacodynamic studies and RNA sequencing (RNA-seq) were conducted 24 and 144 hours after single-agent or combination treatment. Effects on vascular development were studied in Matrigel plugs implanted in mice. The interaction between binary combinations was examined in vitro. Results: Eribulin combined with irinotecan was more effective than vincristine–irinotecan in 6 of 12 models. Pharmacodynamic markers induced by eribulin (phospho-histone H3) and irinotecan (γ-H2A.X) were abrogated in combination-treated tumors. The predominant RNA-seq signature in combination-treated tumors was activation of the TP53 pathway with increased nuclear TP53. Massive apoptosis was observed 24 hours only after treatment with the eribulin combination. In vitro, neither combination showed interaction using combination index analysis. Eribulin alone and the combination caused alterations in developing vasculature. Conclusions: The eribulin combination is very active in these xenograft models, but not synergistic in vitro. The combination reduced pharmacodynamic markers indicative of single-agent mechanisms but in tumors, dramatically activated the TP53 pathway. Although a mechanism for in vivo synergy requires further study, it is possible that eribulin-induced inhibition of microtubule dynamics enhances irinotecan-induced nuclear accumulation of TP53, leading to rapid cell death.

PURPOSE Medical students are particularly vulnerable to occupational exposures to blood-borne pathogens because of their inexperience. Although exposure rates for medical students remain high, they often do not report such incidents or seek the proper medical care. The authors describe and evaluate an intervention at the Yale University School of Medicine to prevent and manage occupational exposures among medical students. METHOD Since 2001, students have met with key faculty during orientation and again before clinical clerkships to discuss the circumstances under which most exposures occur, examine the equipment used to draw blood and start IVs, and review instructions about postexposure management. They are also given a laminated card summarizing this information. In 2010 and 2011, the authors surveyed graduating students about their experiences. RESULTS Two hundred twenty-five of 245 (92%) students responded to the survey, and 82 (36%) had experienced 103 exposures. Forty-seven of those 82 (57%) students reported their exposure, 52 (56%) had the laminated card on them at the time of the incident, and 15 (18%) started postexposure prophylaxis. The most common reasons students cited for not reporting an incident were a low-risk exposure, a sense of embarrassment, or perceived difficulties in getting care. CONCLUSIONS The authors recommend continuing to educate medical students about the importance of reporting exposures and seeking the proper care. They also recommend educating physicians and residents in an attempt to change the environment around exposures so that medical students no longer feel discouraged from reporting incidents.

The Yale Medical Orchestra displayed exceptional talent and inspiration as it performed a timeless composition to celebrate Yale School of Medicine's bicentennial anniversary during a December 2010 concert. Under the leadership of musical directors Robert Smith and Adrian Slywotzky, the richly emotional meditations of Mendelssohn, Dvorak, Schubert, and Yale's own Thomas C. Duffy filled the minds and hearts of an audience as diverse as the orchestra. I intend to retrace the steps of that melodic journey in this essay, fully aware of the limits imposed on me to recreate the aural art form through the medium of text. While these symbols can be pale representations of the beauty and complexity of the music, I hope they will be the building blocks for the emotional experience of the audience. I describe the works' inception and their salient musical features and then review what we know about the effects of melody, meter, and timbre on our brains. My intentions are to provide evidence to encourage the further use of music as a tool in medical practice, provide interest in the works explored by the Yale orchestra, support the orchestra itself, and investigate a personal passion.