Impact of Obesity in Patients with Candida Bloodstream Infections: A Retrospective Cohort Study.

BACKGROUND: Candida species are responsible for 15% of bloodstream infections, leading to prolonged hospitalizations and increased mortality. With the rise in obesity, antifungal dosing is unclear. The purpose of this study was to determine differences in clinical outcomes between obese versus non-obese patients with Candida bloodstream infections. METHODS: This retrospective cohort included adult patient's first episode of Candida bloodstream infection treated with ≥ 48 h of antifungal therapy between 1 June 2013 and 31 August 2019. Patients were excluded for: dual systemic antifungal therapy, polymicrobial infections, or chronic candidiasis. The primary outcome was infection-related length of stay. Secondary outcomes included: time to candidemia resolution, 30-day readmission rates, and in-hospital mortality. RESULTS: Eighty patients were included (28 obese; 52 non-obese). Most were male (55%); median age was 54 years. Median BMI and weight were 36.3 kg/m2 and 103 kg versus 20.4 kg/m2 and 61 kg, respectively (p < 0.01). Baseline characteristics were comparable. C. albicans was isolated in 37.5% of cultures and C. glabrata in 30%. Micafungin was utilized empirically in 72.5% of patients; obese patients received definitive micafungin more frequently (57.1% vs. 21.2%; p < 0.01) and were treated longer (13 versus 10 days; p = 0.04). Infection-related length of stay was 19 days in the obese patients and 13 days in the non-obese patients (p = 0.05). Non-obese patients had a shorter duration of candidemia (5 versus 6 days; p = 0.02). In-hospital mortality was numerically higher in obese patients (21.4% versus 13.5%; p = 0.36). There were no differences in 30-day readmissions between groups. CONCLUSIONS: Worse clinical outcomes were observed for obese versus non-obese patients. Further clinical research is warranted.

Chirality at two-dimensional surfaces: A perspective from small molecule alcohol assembly on Au(111).

The delicate balance between hydrogen bonding and van der Waals interactions determines the stability, structure, and chirality of many molecular and supramolecular aggregates weakly adsorbed on solid surfaces. Yet the inherent complexity of these systems makes their experimental study at the molecular level very challenging. In this quest, small alcohols adsorbed on metal surfaces have become a useful model system to gain fundamental insight into the interplay of such molecule-surface and molecule-molecule interactions. Here, through a combination of scanning tunneling microscopy and density functional theory, we compare and contrast the adsorption and self-assembly of a range of small alcohols from methanol to butanol on Au(111). We find that longer chained alcohols prefer to form zigzag chains held together by extended hydrogen bonded networks between adjacent molecules. When alcohols bind to a metal surface datively via one of the two lone electron pairs of the oxygen atom, they become chiral. Therefore, the chain structures are formed by a hydrogen-bonded network between adjacent molecules with alternating adsorbed chirality. These chain structures accommodate longer alkyl tails through larger unit cells, while the position of the hydroxyl group within the alcohol molecule can produce denser unit cells that maximize intermolecular interactions. Interestingly, when intrinsic chirality is introduced into the molecule as in the case of 2-butanol, the assembly changes completely and square packing structures with chiral pockets are observed. This is rationalized by the fact that the intrinsic chirality of the molecule directs the chirality of the adsorbed hydroxyl group meaning that heterochiral chain structures cannot form. Overall this study provides a general framework for understanding the effect of simple alcohol molecular adstructures on hydrogen bonded aggregates and paves the way for rationalizing 2D chiral supramolecular assembly.

The impact of emotion on numerical estimation: A developmental perspective.

Recent literature has revealed underestimation effects in numerical judgments when adult participants are presented with emotional stimuli (as opposed to neutral). Whether these numerical biases emerge early in development however, or instead reflect overt, learned responses to emotional stimuli across development are unclear. Moreover, reported links between numerical acuity and mathematics achievement point to the importance of exploring how numerical approximation abilities in childhood may be influenced in real-world affective contexts. In this study, children (aged 6-10 years) and adults were presented with happy and neutral facial stimuli in the context of a numerical bisection task. Results reveal that children, like adults, underestimate number following emotional (i.e., happy) faces (relative to neutral). However, children's, but not adult's, responses were also significantly more precise following emotional stimuli. In a second experiment, adult judgments revealed a similar increase in precision following emotional stimuli when numerical discriminations were more challenging (involving larger sets). Together, results are the first to reveal children, like adults, underestimate number in the context of emotional stimuli and this underestimation bias is accompanied with enhanced response precision.

Water-Ice Analogues of Polycyclic Aromatic Hydrocarbons: Water Nanoclusters on Cu(111).

Water has an incredible ability to form a rich variety of structures, with 16 bulk ice phases identified, for example, as well as numerous distinct structures for water at interfaces or under confinement. Many of these structures are built from hexagonal motifs of water molecules, and indeed, for water on metal surfaces, individual hexamers of just six water molecules have been observed. Here, we report the results of low-temperature scanning tunneling microscopy experiments and density functional theory calculations which reveal a host of new structures for water-ice nanoclusters when adsorbed on an atomically flat Cu surface. The H-bonding networks within the nanoclusters resemble the resonance structures of polycyclic aromatic hydrocarbons, and water-ice analogues of inene, naphthalene, phenalene, anthracene, phenanthrene, and triphenylene have been observed. The specific structures identified and the H-bonding patterns within them reveal new insight about water on metals that allows us to refine the so-called "2D ice rules", which have so far proved useful in understanding water-ice structures at solid surfaces.

The interplay of covalency, hydrogen bonding, and dispersion leads to a long range chiral network: The example of 2-butanol.

The assembly of complex structures in nature is driven by an interplay between several intermolecular interactions, from strong covalent bonds to weaker dispersion forces. Understanding and ultimately controlling the self-assembly of materials requires extensive study of how these forces drive local nanoscale interactions and how larger structures evolve. Surface-based self-assembly is particularly amenable to modeling and measuring these interactions in well-defined systems. This study focuses on 2-butanol, the simplest aliphatic chiral alcohol. 2-butanol has recently been shown to have interesting properties as a chiral modifier of surface chemistry; however, its mode of action is not fully understood and a microscopic understanding of the role non-covalent interactions play in its adsorption and assembly on surfaces is lacking. In order to probe its surface properties, we employed high-resolution scanning tunneling microscopy and density functional theory (DFT) simulations. We found a surprisingly rich degree of enantiospecific adsorption, association, chiral cluster growth and ultimately long range, highly ordered chiral templating. Firstly, the chiral molecules acquire a second chiral center when adsorbed to the surface via dative bonding of one of the oxygen atom lone pairs. This interaction is controlled via the molecule's intrinsic chiral center leading to monomers of like chirality, at both chiral centers, adsorbed on the surface. The monomers then associate into tetramers via a cyclical network of hydrogen bonds with an opposite chirality at the oxygen atom. The evolution of these square units is surprising given that the underlying surface has a hexagonal symmetry. Our DFT calculations, however, reveal that the tetramers are stable entities that are able to associate with each other by weaker van der Waals interactions and tessellate in an extended square network. This network of homochiral square pores grows to cover the whole Au(111) surface. Our data reveal that the chirality of a simple alcohol can be transferred to its surface binding geometry, drive the directionality of hydrogen-bonded networks and ultimately extended structure. Furthermore, this study provides the first microscopic insight into the surface properties of this important chiral modifier and provides a well-defined system for studying the network's enantioselective interaction with other molecules.

Ullmann coupling mediated assembly of an electrically driven altitudinal molecular rotor.

Surface-bound molecular rotation can occur with the rotational axis either perpendicular (azimuthal) or parallel (altitudinal) to the surface. The majority of molecular rotor studies involve azimuthal rotors, whereas very few altitudinal rotors have been reported. In this work, altitudinal rotors are formed by means of coupling aryl halides through a surface-mediated Ullmann coupling reaction, producing a reaction state-dependent altitudinal molecular rotor/stator. All steps in the reaction on a Cu(111) surface are visualized by low-temperature scanning tunneling microscopy. The intermediate stage of the coupling reaction is a metal-organic complex consisting of two aryl groups attached to a single copper atom with the aryl rings angled away from the surface. This conformation leads to nearly unhindered rotational motion of ethyl groups at the para positions of the aryl rings. Rotational events of the ethyl group are both induced and quantified by electron tunneling current versus time measurements and are only observed for the intermediate structure of the Ullmann coupling reaction, not the starting material or finished product in which the ethyl groups are static. We perform an extensive set of inelastic electron tunneling driven rotation experiments that reveal that torsional motion around the ethyl group is stimulated by tunneling electrons in a one-electron process with an excitation energy threshold of 45 meV. This chemically tunable system offers an ideal platform for examining many fundamental aspects of the dynamics of chemically tunable molecular rotor and motors.

Enhancement of low-energy electron emission in 2D radioactive films.

High-energy radiation has been used for decades; however, the role of low-energy electrons created during irradiation has only recently begun to be appreciated. Low-energy electrons are the most important component of radiation damage in biological environments because they have subcellular ranges, interact destructively with chemical bonds, and are the most abundant product of ionizing particles in tissue. However, methods for generating them locally without external stimulation do not exist. Here, we synthesize one-atom-thick films of the radioactive isotope (125)I on gold that are stable under ambient conditions. Scanning tunnelling microscopy, supported by electronic structure simulations, allows us to directly observe nuclear transmutation of individual (125)I atoms into (125)Te, and explain the surprising stability of the 2D film as it underwent radioactive decay. The metal interface geometry induces a 600% amplification of low-energy electron emission (<10 eV; ref. ) compared with atomic (125)I. This enhancement of biologically active low-energy electrons might offer a new direction for highly targeted nanoparticle therapies.

Impact of branching on the supramolecular assembly of thioethers on Au(111).

Alkanethiolate monolayers are one of the most comprehensively studied self-assembled systems due to their ease of preparation, their ability to be functionalized, and the opportunity to control their thickness perpendicular to the surface. However, these systems suffer from degradation due to oxidation and defects caused by surface etching and adsorbate rotational boundaries. Thioethers offer a potential alternative to thiols that overcome some of these issues and allow dimensional control of self-assembly parallel to the surface. Thioethers have found uses in surface modification of nanoparticles, and chiral thioethers tethered to catalytically active surfaces have been shown to enable enantioselective hydrogenation. However, the effect of structural, chemical, and chiral modifications of the alkyl chains of thioethers on their self-assembly has remained largely unstudied. To elucidate how molecular structure, particularly alkyl branching and chirality, affects molecular self-assembly, we compare four related thioethers, including two pairs of structural isomers. The self-assembly of structural isomers N-butyl methyl sulfide and tert-butyl methyl sulfide was studied with high resolution scanning tunneling microscopy (STM); our results indicate that both molecules form highly ordered arrays despite the bulky tert-butyl group. We also investigated the effect of intrinsic chirality in the alkyl tails on the adsorption and self-assembly of butyl sec-butyl sulfide (BSBS) with STM and density functional theory and contrast our results to its structural isomer, dibutyl sulfide. Calculations provide the relative stability of the four stereoisomers of BSBS and STM imaging reveals two prominent monomer forms. Interestingly, the racemic mixture of BSBS is the only thioether we have examined to date that does not form highly ordered arrays; we postulate that this is due to weak enantiospecific intermolecular interactions that lead to the formation of energetically similar but structurally different assemblies. Furthermore, we studied all of the molecules in their monomeric molecular rotor form, and the surface-adsorbed chirality of the three asymmetric thioethers is distinguishable in STM images.

Structure and energetics of hydrogen-bonded networks of methanol on close packed transition metal surfaces.

Methanol is a versatile chemical feedstock, fuel source, and energy storage material. Many reactions involving methanol are catalyzed by transition metal surfaces, on which hydrogen-bonded methanol overlayers form. As with water, the structure of these overlayers is expected to depend on a delicate balance of hydrogen bonding and adsorbate-substrate bonding. In contrast to water, however, relatively little is known about the structures methanol overlayers form and how these vary from one substrate to another. To address this issue, herein we analyze the hydrogen bonded networks that methanol forms as a function of coverage on three catalytically important surfaces, Au(111), Cu(111), and Pt(111), using a combination of scanning tunneling microscopy and density functional theory. We investigate the effect of intermolecular interactions, surface coverage, and adsorption energies on molecular assembly and compare the results to more widely studied water networks on the same surfaces. Two main factors are shown to direct the structure of methanol on the surfaces studied: the surface coverage and the competition between the methanol-methanol and methanol-surface interactions. Additionally, we report a new chiral form of buckled hexamer formed by surface bound methanol that maximizes the interactions between methanol monomers by sacrificing interactions with the surface. These results serve as a direct comparison of interaction strength, assembly, and chirality of methanol networks on Au(111), Cu(111), and Pt(111) which are catalytically relevant for methanol oxidation, steam reforming, and direct methanol fuel cells.

Hydrogen Dissociation, Spillover, and Desorption from Cu-Supported Co Nanoparticles.

Co-Cu nanoparticles have recently been explored for Fischer-Tropsch synthesis (FTS) as a way to combine the long chain selectivity of Co with Cu's activity for alcohol formation in order to synthesize oxygenated transportation fuels. Depending on particle size, hydrogen dissociation can be a rate-determining step in cobalt-catalyzed FTS. To understand the fundamentals of uptake and release of hydrogen from the Co/Cu bimetallic system, we prepared well-defined Co nanoparticles on Cu(111). We demonstrate that hydrogen spills over from dissociation sites on the Co nanoparticles to the Cu(111) surface via the Co-Cu interface and that desorption of H occurs at a temperature that is lower than from Co or Cu alone, which we attribute to the Co-Cu interface sites. From this data, we have constructed an energy landscape for the facile dissociation, spillover, and desorption of hydrogen on the Co-Cu bimetallic system.

Atomic-scale insight into the formation, mobility and reaction of Ullmann coupling intermediates.

The Ullmann reaction of bromobenzene, the simplest coupling reagent, to form biphenyl on a Cu surface proceeds via a highly mobile organometallic intermediate in which two phenyl groups extract and bind a single surface Cu atom.

Molecular-scale perspective of water-catalyzed methanol dehydrogenation to formaldehyde.

Methanol steam reforming is a promising reaction for on-demand hydrogen production. Copper catalysts have excellent activity and selectivity for methanol conversion to hydrogen and carbon dioxide. This product balance is dictated by the formation and weak binding of formaldehyde, the key reaction intermediate. It is widely accepted that oxygen adatoms or oxidized copper are required to activate methanol. However, we show herein by studying a well-defined metallic copper surface that water alone is capable of catalyzing the conversion of methanol to formaldehyde. Our results indicate that six or more water molecules act in concert to deprotonate methanol to methoxy. Isolated palladium atoms in the copper surface further promote this reaction. This work reveals an unexpected role of water, which is typically considered a bystander in this key chemical transformation.

Controlling a spillover pathway with the molecular cork effect.

Spillover of reactants from one active site to another is important in heterogeneous catalysis and has recently been shown to enhance hydrogen storage in a variety of materials. The spillover of hydrogen is notoriously hard to detect or control. We report herein that the hydrogen spillover pathway on a Pd/Cu alloy can be controlled by reversible adsorption of a spectator molecule. Pd atoms in the Cu surface serve as hydrogen dissociation sites from which H atoms can spillover onto surrounding Cu regions. Selective adsorption of CO at these atomic Pd sites is shown to either prevent the uptake of hydrogen on, or inhibit its desorption from, the surface. In this way, the hydrogen coverage on the whole surface can be controlled by molecular adsorption at a minority site, which we term a 'molecular cork' effect. We show that the molecular cork effect is present during a surface catalysed hydrogenation reaction and illustrate how it can be used as a method for controlling uptake and release of hydrogen in a model storage system.

Visualization of compression and spillover in a coadsorbed system: syngas on cobalt nanoparticles.

Competitive adsorption and lateral pressure between surface-bound intermediates are important effects that dictate chemical reactivity. Lateral, or two-dimensional, pressure is known to promote reactivity by lowering energetic barriers and increasing conversion to products. We examined the coadsorption of CO and H2, the two reactants in the industrially important Fischer-Tropsch synthesis, on Co nanoparticles to investigate the effect of two-dimensional pressure. Using scanning tunneling microscopy, we directly visualized the coadsorption of H and CO on Co, and we found that the two adsorbates remain in segregated phases. CO adsorbs on the Co nanoparticles via spillover from the Cu(111) support, and when deposited onto preadsorbed adlayers of H, CO exerts two-dimensional pressure on H, compressing it into a higher-density, energetically less-preferred structure. By depositing excess CO, we found that H on the Co surface is forced to spill over onto the Cu(111) support. Thus, spillover of H from Co onto Cu, where it would not normally reside due to the high activation barrier, is preferred over desorption. We corroborated the mechanism of this spillover-induced displacement by calculating the relevant energetics using density functional theory, which show that the displacement of H from Co is compensated for by the formation of strong CO-Co bonds. These results may have significant ramifications for Fischer-Tropsch synthesis kinetics on Co, as the segregation of CO and H, as well as the displacement of H by CO, limits the interface between the two molecules.

Quantum tunneling enabled self-assembly of hydrogen atoms on Cu(111).

Atomic and molecular self-assembly are key phenomena that underpin many important technologies. Typically, thermally enabled diffusion allows a system to sample many areas of configurational space, and ordered assemblies evolve that optimize interactions between species. Herein we describe a system in which the diffusion is quantum tunneling in nature and report the self-assembly of H atoms on a Cu(111) surface into complex arrays based on local clustering followed by larger scale islanding of these clusters. By scanning tunneling microscope tip-induced scrambling of H atom assemblies, we are able to watch the atomic scale details of H atom self-assembly in real time. The ordered arrangements we observe are complex and very different from those formed by H on other metals that occur in much simpler geometries. We contrast the diffusion and assembly of H with D, which has a much slower tunneling rate and is not able to form the large islands observed with H over equivalent time scales. Using density functional theory, we examine the interaction of H atoms on Cu(111) by calculating the differential binding energy as a function of H coverage. At the temperature of the experiments (5 K), H(D) diffusion by quantum tunneling dominates. The quantum-tunneling-enabled H and D diffusion is studied using a semiclassically corrected transition state theory coupled with density functional theory. This system constitutes the first example of quantum-tunneling-enabled self-assembly, while simultaneously demonstrating the complex ordering of H on Cu(111), a catalytically relevant surface.

Isolated metal atom geometries as a strategy for selective heterogeneous hydrogenations.

Facile dissociation of reactants and weak binding of intermediates are key requirements for efficient and selective catalysis. However, these two variables are intimately linked in a way that does not generally allow the optimization of both properties simultaneously. By using desorption measurements in combination with high-resolution scanning tunneling microscopy, we show that individual, isolated Pd atoms in a Cu surface substantially lower the energy barrier to both hydrogen uptake on and subsequent desorption from the Cu metal surface. This facile hydrogen dissociation at Pd atom sites and weak binding to Cu allow for very selective hydrogenation of styrene and acetylene as compared with pure Cu or Pd metal alone.

Rediscovering cobalt's surface chemistry.

Cobalt is an active metal for a variety of commercially and environmentally significant heterogeneously catalysed processes. Despite its importance, Co's surface chemistry is less studied compared to other key industrial catalyst metals. This stems in part from the difficulties associated with single crystal preparation and stability. Recent advances in scanning probe microscopy have enabled the atomic scale study of the structural, electronic, and magnetic properties of well-defined Co nanoparticles on metal substrates. Such systems offer an excellent platform to investigate the adsorption, diffusion, dissociation, and reaction of catalytically relevant molecules. Here we discuss the current understanding of metal-supported Co nanoparticles, review the limited literature on molecular adsorption, and suggest ways that they can be used to explore Co's rich surface chemistry. Our discussion is accompanied by new high resolution scanning tunnelling microscopy data from our group, which illustrate some of the interesting properties of these complex systems.