Regioselective Partial Hydrogenation and Deuteration of Tetracyclic (Hetero)aromatic Systems Using a Simple Heterogeneous Catalyst.

The introduction of added '3-dimensionality' through late-stage functionalisation of extended (hetero)aromatic systems is a powerful synthetic approach. The abundance of starting materials and cross-coupling methodologies to access the precursors allows for highly diverse products. Subsequent selective partial reduction can alter the core structure in a manner of interest to medicinal chemists. Herein, we describe the precise, partial reduction of multicyclic heteroaromatic systems using a simple heterogeneous catalyst. The approach can be extended to introduce deuterium (again at late-stage). Excellent yields can be obtained using simple reaction conditions.

Guides and cheats: producer-scrounger dynamics in the human-honeyguide mutualism.

Foraging animals commonly choose whether to find new food (as 'producers') or scavenge from others (as 'scroungers'), and this decision has ecological and evolutionary consequences. Understanding these tactic decisions is particularly vital for naturally occurring producer-scrounger systems of economic importance, because they determine the system's productivity and resilience. Here, we investigate how individuals' traits predict tactic decisions, and the consistency and pay-offs of these decisions, in the remarkable mutualism between humans (Homo sapiens) and greater honeyguides (Indicator indicator). Honeyguides can either guide people to bees' nests and eat the resulting beeswax (producing), or scavenge beeswax (scrounging). Our results suggest that honeyguides flexibly switched tactics, and that guiding yielded greater access to the beeswax. Birds with longer tarsi scrounged more, perhaps because they are more competitive. The lightest females rarely guided, possibly to avoid aggression, or because genetic matrilines may affect female body mass and behaviour in this species. Overall, aspects of this producer-scrounger system probably increase the productivity and resilience of the associated human-honeyguide mutualism, because the pay-offs incentivize producing, and tactic-switching increases the pool of potential producers. Broadly, our findings suggest that even where tactic-switching is prevalent and producing yields greater pay-offs, certain phenotypes may be predisposed to one tactic.

When wax wanes: competitors for beeswax stabilize rather than jeopardize the honeyguide-human mutualism.

Many mutualisms are exploited by third-party species, which benefit without providing anything in return. Exploitation can either destabilize or promote mutualisms, via mechanisms that are highly dependent on the ecological context. Here we study a remarkable bird-human mutualism, in which wax-eating greater honeyguides (Indicator indicator) guide humans (Homo sapiens) to wild bees' nests, in an exchange of knowledge about the location of nests for access to the wax combs inside. We test whether the depletion of wax by mammalian and avian exploiter species either threatens or stabilizes the mutualism. Using camera traps, we monitored feeding visits to wax comb made available following honey harvests. We found that greater honeyguides face competition for wax from conspecifics and nine exploiter species, five of which were not previously known to consume wax. Our results support the hypothesis that heterospecific exploiters stabilize the mutualism, because wax depletion by these competitors probably limits feeding opportunities for conspecific exploiters, favouring the early-arriving individual that guided humans to the bees' nest. These findings highlight the importance of the ecological context of species interactions and provide further evidence for how mutualisms can persist because of, and not in spite of, exploitation by third-party species.

Total Synthesis and Prediction of Ulodione Natural Products Guided by DFT Calculations.

A biomimetic synthetic strategy has resulted in a two-step total synthesis of (±)-ulodione A and the prediction of two potential natural products, (±)-ulodiones C and D. This work was guided by computational investigations into the selectivity of a proposed biosynthetic Diels-Alder dimerization, which was then utilized in the chemical synthesis. This work highlights how biosynthetic considerations can both guide the design of efficient synthetic strategies and lead to the anticipation of new natural products.

Reduced Recombination and Capacitor-like Charge Buildup in an Organic Heterojunction.

Organic photovoltaic (OPV) efficiencies continue to rise, raising their prospects for solar energy conversion. However, researchers have long considered how to suppress the loss of free carriers by recombination-poor diffusion and significant Coulombic attraction can cause electrons and holes to encounter each other at interfaces close to where they were photogenerated. Using femtosecond transient spectroscopies, we report the nanosecond grow-in of a large transient Stark effect, caused by nanoscale electric fields of ∼487 kV/cm between photogenerated free carriers in the device active layer. We find that particular morphologies of the active layer lead to an energetic cascade for charge carriers, suppressing pathways to recombination, which is ∼2000 times less than predicted by Langevin theory. This in turn leads to the buildup of electric charge in donor and acceptor domains-away from the interface-resistant to bimolecular recombination. Interestingly, this signal is only experimentally obvious in thick films due to the different scaling of electroabsorption and photoinduced absorption signals in transient absorption spectroscopy. Rather than inhibiting device performance, we show that devices up to 600 nm thick maintain efficiencies of >8% because domains can afford much higher carrier densities. These observations suggest that with particular nanoscale morphologies the bulk heterojunction can go beyond its established role in charge photogeneration and can act as a capacitor, where adjacent free charges are held away from the interface and can be protected from bimolecular recombination.

A systematic review of vertical integration and quality of care, efficiency, and patient-centered outcomes.

BACKGROUND: Small independent practices are increasingly giving way to more complex affiliations between provider organizations and hospital systems. There are several ways in which vertically integrated health systems could improve quality and lower the costs of care. But there are also concerns that integrated systems may increase the price and costs of care without commensurate improvements in quality and outcomes. PURPOSE: Despite a growing body of research on vertically integrated health systems, no systematic review that we know of compares vertically integrated health systems (defined as shared ownership or joint management of hospitals and physician practices) to nonintegrated hospitals or physician practices. METHODS: We conducted a systematic search of the literature published from January 1996 to November 2016. We considered articles for review if they compared the performance of a vertically integrated health system and examined an outcome related to quality of care, efficiency, or patient-centered outcomes. RESULTS: Database searches generated 7,559 articles, with 29 articles included in this review. Vertical integration was associated with better quality, often measured as optimal care for specific conditions, but showed either no differences or lower efficiency as measured by utilization, spending, and prices. Few studies evaluated a patient-centered outcome; among those, most examined mortality and did not identify any effects. Across domains, most studies were observational and did not address the issue of selection bias. PRACTICE IMPLICATIONS: Recent evidence suggests the trend toward vertical integration will likely continue as providers respond to changing payment models and market factors. A growing body of research on comparative health system performance suggests that integration of physician practices with hospitals might not be enough to achieve higher-value care. More information is needed to identify the health system attributes that contribute to improved outcomes, as well as which policy levers can minimize anticompetitive effects and maximize the benefits of these affiliations.

An improved synthesis of adefovir and related analogues.

An improved synthesis of the antiviral drug adefovir is presented. Problems associated with current routes to adefovir include capricious yields and a reliance on problematic reagents and solvents, such as magnesium tert-butoxide and DMF, to achieve high conversions to the target. A systematic study within our laboratory led to the identification of an iodide reagent which affords higher yields than previous approaches and allows for reactions to be conducted up to 10 g in scale under milder conditions. The use of a novel tetrabutylammonium salt of adenine facilitates alkylations in solvents other than DMF. Additionally, we have investigated how regioselectivity is affected by the substitution pattern of the nucleobase. Finally, this chemistry was successfully applied to the synthesis of several new adefovir analogues, highlighting the versatility of our approach.

Emissive Molecular Aggregates and Energy Migration in Luminescent Solar Concentrators.

Luminescent solar concentrators (LSCs) are light harvesting devices that are ideally suited to light collection in the urban environment where direct sunlight is often not available. LSCs consist of highly luminescent compounds embedded or coated on a transparent substrate that absorb diffuse or direct solar radiation over a large area. The resulting luminescence is trapped in the waveguide by total internal reflection to the thin edges of the substrate where the concentrated light can be used to improve the performance of photovoltaic devices. The concept of LSCs has been around for several decades, and yet the efficiencies of current devices are still below expectations for commercial viability. There are two primary challenges when designing new chromophores for LSC applications. Reabsorption of dye emission by chromophores within the waveguide is a significant loss mechanism attenuating the light output of LSCs. Concentration quenching, particularly in organic dye systems, restricts the quantity of chromophores that can be incorporated in the waveguide thus limiting the light absorbed by the LSC. Frequently, a compromise between increased light harvesting of the incident light and decreasing emission quantum yield is required for most organic chromophore-based systems due to concentration quenching. The low Stokes shift of common organic dyes used in current LSCs also imposes another optimization problem. Increasing light absorption of LSCs based on organic dyes to achieve efficient light harvesting also enhances reabsorption. Ideally, a design strategy to simultaneously optimize light harvesting, concentration quenching, and reabsorption of LSC chromophores is clearly needed to address the significant losses in LSCs. Over the past few years, research in our group has targeted novel dye structures that address these primary challenges. There is a common perception that dye aggregates are to be avoided in LSCs. It became apparent in our studies that aggregates of chromophores exhibiting aggregation-induced emission (AIE) behavior are attractive candidates for LSC applications. Strategic application of AIE chromophores has led to the development of the first organic-based transparent solar concentrator that harvests UV light as well as the demonstration of reabsorption reduction by taking advantage of energy migration processes between chromophores. Further developments led us to the application of perylene diimides using an energy migration/energy transfer approach. To prevent concentration quenching, a molecularly insulated perylene diimide with bulky substituents attached to the imide positions was designed and synthesized. By combining the insulated perylene diimide with a commercial perylene dye as an energy donor-acceptor emitter pair, detrimental luminescence reabsorption was reduced while achieving a high chromophore concentration for efficient light absorption. This Account reviews and reinspects some of our recent work and the improvements in the field of LSCs.

Door to Needle Time over Telestroke-A Comprehensive Stroke Center Experience.

BACKGROUND: The implementation of telestroke programs has allowed patients living in rural areas suffering from acute ischemic stroke to receive expert acute stroke consultation and intravenous Alteplase (tPA). The purpose of this study is to compare door to needle (DTN) time when tPA is administered at telestroke sites (spokes) through telestroke consultations compared to tPA administration at the comprehensive stroke center (hub). METHODS: Data on all patients who received intravenous tPA at the hub and spoke hospitals through a large telestroke program between May 2008 and December 2016 were collected. Baseline characteristics were compared between the two groups, and the percentage of patients meeting DTN guidelines was compared between the hub and spoke hospitals during the study period. Comparison of DTN before and after the implementation of a quality improvement project was performed. RESULTS: A total of 1,665 patients received tPA at either the spoke (n = 1,323) or the hub (n = 342) during the study period. Baseline characteristics were comparable in both treatment groups. Before the intervention, DTN time <60 min was achieved in 88% of the hub patients versus 38% of the spoke patients. This difference between the two groups decreased by 35 percentage points, controlling for year (p = 0.0018) after the interventions. CONCLUSION: Overall, DTN is longer at the spoke hospitals compared to the hub hospital. This can be improved by various interventions that target quality, training, education, and improving the comfort level of the staff at partner hospitals when treating acute stroke patients.

Medical University of South Carolina Telestroke: A Telemedicine Facilitated Network for Stroke Treatment in South Carolina-A Progress Report.

BACKGROUND: Patients in rural communities lack access to acute stroke therapies. Rapid administration of lytic therapy increases the likelihood of favorable functional outcome in acute ischemic stroke (AIS). At the Medical University of South Carolina (MUSC), we implemented a Web-based telestroke program that allows patients presenting with AIS at a rural hospital to receive expert stroke consultation within minutes. This increases their chances of receiving lytic therapy, and therefore increases the likelihood of good functional outcome. OBJECTIVES: Our study aims to provide an update on how our telestroke program had developed and the rate and safety of intravenous (IV) alteplase administration through telestroke. METHODS: Data were collected on all patients evaluated through the MUSC Telestroke program from May 2008 through April 2014. Collected data included National Institutes of Health Stroke Scale (NIHSS) on presentation, number of IV alteplase administrations, number of patients transferred to MUSC, number of mechanical thrombectomies performed on transferred patients, rate of symptomatic intracerebral hemorrhages (sICHs), and discharge location. RESULTS: A total of 7,694 consults were performed during the study period. Of them 3,795 (49.2%) patients were diagnosed with ischemic stroke, of those 1,324 (34.8%) received IV alteplase. A total of 1,282 patients were transferred to MUSC for further care. From November 2014 to April 2016, 56 patients received mechanical thrombectomy. sICH occurred in 33 patients who received alteplase, and in 5 patients receiving a combination of IV and intraarterial thrombolysis. Over the study period, the number of participating sites increased from 6 to 19 sites. The percentage of transfers to MUSC decreased from 36% to 14%. CONCLUSIONS: Our study shows that our telestroke program had evolved over time to involve more sites throughout the state of South Carolina. Post-IV alteplase sICH was low and within the expected range.

A Green Route to Conjugated Polyelectrolyte Interlayers for High-Performance Solar Cells.

Synthesis of fluorene-based conjugated polyelectrolytes was achieved via Suzuki polycondensation in water and completely open to air. The polyelectrolytes were conveniently purified by dialysis and analysis of the materials showed properties expected for fluorene-based conjugated polyelectrolytes. The materials were then employed in solar cell devices as an interlayer in conjunction with ZnO. The double interlayer led to enhanced power conversion efficiency of 10.75 % and 15.1 % for polymer and perovskite solar cells, respectively.

Separation and identification of indene-C70 bisadduct isomers.

Following an initial work on the isolation of a single geometric isomer from an indene-C70 bisadduct (IC70BA) mixture, we report the full fractionation and identification of the bisadduct species in the material. Eleven fractions of IC70BA isomers were separated by high-performance liquid chromatography. A number of fractions contained relatively pure isomer species and their configuration were deduced using a variety of analytical techniques including (1)H and (13)C NMR and UV-vis spectroscopy. The electrochemical properties and the organic solar cell device performance were investigated for fractions where a reasonable quantity of sample could be isolated.

High performance p-type molecular electron donors for OPV applications via alkylthiophene catenation chromophore extension.

The synthesis of key 4-alkyl-substituted 5-(trimethylsilyl)thiophene-2-boronic acid pinacol esters 3 allowed a simplified alkylthiophene catenation process to access bis-, ter-, quater-, and quinquethiophene π-bridges for the synthesis of acceptor-π-bridge-donor- π-bridge-acceptor (A-π-D-π-A) electron donor molecules. Based on the known benzodithiophene-terthiophene-rhodanine (BTR) material, the BXR series of materials, BMR (X = M, monothiophene), BBR (X = B, bithiophene), known BTR (X = T, terthiophene), BQR (X = Q, quaterthiophene), and BPR (X = P(penta), quinquethiophene) were synthesised to examine the influence of chromophore extension on the device performance and stability for OPV applications. The BTxR (x = 4, butyl, and x = 8, octyl) series of materials were synthesised by varying the oligothiophene π-bridge alkyl substituent to examine structure-property relationships in OPV device performance. The devices assembled using electron donors with an extended chromophore (BQR and BPR) are shown to be more thermally stable than the BTR containing devices, with un-optimized efficiencies up to 9.0% PCE. BQR has been incorporated as a secondary donor in ternary blend devices with PTB7-Th resulting in high-performance OPV devices with up to 10.7% PCE.

Organic Photovoltaic Materials--Design, Synthesis and Scale-Up.

This account describes the work of our group in the area of organic photovoltaics in the past six years. The emphasis is on our experiences in the development of the organic materials, their characterization, scale-up and application in devices. We share our insight into the relationship between synthetic methods, molecular properties, bulk material properties and device performance.

Regioselective synthesis of fullerene multiadducts via tether-directed 1,3-dipolar cycloaddition.

The regioselective synthesis of fullerene multiadducts was achieved from commercially available reagents in one pot over two steps. The configuration of the isolated regioisomers was determined using various NMR methods, UV-vis spectroscopy and electrochemical analysis with the structure of one isomer confirmed by single crystal X-ray analysis. Interesting variation in regioselectivity was observed when different amino acid reagents were used in the reactions. Theoretical calculations and additional experiments, such as deuterium exchange, led to a proposed mechanism for the regioselective product formation.

Hospital outpatient department billing is a poor indicator of primary care practice integration with hospital systems.

OBJECTIVE: To test the reliability of Medicare claims in measuring vertical integration. We assess the accuracy of a commonly used measure of integration, primary care physician (PCP) practices billing Medicare as a hospital outpatient department (HOPD) in claims. DATA SOURCES AND STUDY SETTING: Medicare fee-for-service claims, IQVIA, and CPC+ practice surveys for this study. STUDY DESIGN: We compare measures of integration from Medicare claims to self-reported indicators of integration from IQVIA and a survey of CPC+ participating practice sites. DATA COLLECTION/EXTRACTION METHODS: We measure integration by using site-of-service billing in the 100% sample of Medicare Carrier claims from 2017-2020. In the IQVIA SK&A (2017-2018), OneKey (2019-2020), and practice survey data (2017-2019), we use self-reported responses to measure integration. PRINCIPAL FINDINGS: We find that currently most PCP practices sites that report themselves as being integrated with a health system do not bill as an HOPD. In 2017, 11% of CPC+ practices were identified as being vertically integrated in claims, while the equivalent numbers in SK&A and surveys were 52% and 54% integration, respectively. A t-test found that both datasets significantly differed from claims (Survey: 41.3%-45.1%; SK&A: 45.3%-51.1%); this gap persists in 2018-2019. CONCLUSION: Measuring physician-hospital vertical integration accurately is integral to determining consolidation. The overwhelming majority of PCP practice sites not billing as an HOPD may reflect Medicare regulatory changes that have reduced the financial incentives for doing so. These findings have implications for researchers that study the growth in PCP-hospital integration in health care markets.

Stereoretentive enantioconvergent reactions.

Enantioconvergent reactions are pre-eminent in contemporary asymmetric synthesis as they convert both enantiomers of a racemic starting material into a single enantioenriched product, thus avoiding the maximum 50% yield associated with resolutions. All currently known enantioconvergent processes necessitate the loss or partial loss of the racemic substrate's stereochemical information, thus limiting the potential substrate scope to molecules that contain labile stereogenic units. Here we present an alternative approach to enantioconvergent reactions that can proceed with full retention of the racemic substrate's configuration. This uniquely stereo-economic approach is possible if the two enantiomers of a racemic starting material are joined together to form one enantiomer of a non-meso product. Experimental validation of this concept is presented using two distinct strategies: (1) a direct asymmetric coupling approach, and (2) a multicomponent approach, which exhibits statistical amplification of enantiopurity. Thus, the established dogma that enantioconvergent reactions require substrates that contain labile stereogenic units is shown to be incorrect.

LARP-assisted synthesis of CsBi3I10 perovskite for efficient lead-free solar cells.

Bismuth-based perovskites are an important class of materials in the fabrication of lead-free perovskite solar cells. Bi-based Cs3Bi2I9 and CsBi3I10 perovskites are getting much attention due to their appropriate bandgap values of 2.05 eV and 1.77 eV, respectively. However, the device optimisation process plays a key role in controlling the film quality and the performance of perovskite solar cells. Hence, a new strategy to improve crystallization as well as the thin film quality is equally important to develop efficient perovskite solar cells. Herein, an attempt was made to prepare the Bi-based Cs3Bi2I9 and CsBi3I10 perovskites via the ligand-assisted re-precipitation approach (LARP). The physical, structural, and optical properties were investigated on perovskite films deposited by the solution process for solar cell applications. Cs3Bi2I9 and CsBi3I10-based perovskite-based solar cells were fabricated using the device architecture of ITO/NiO x /perovskite layer/PC61BM/BCP/Ag. The device fabricated with CsBi3I10 showed the best power conversion efficiency (PCE) of 2.3% with an improved fill factor (FF) of 69%, V OC of 0.79 V, and J SC of 4.2 mA cm-2 compared to the Cs3Bi2I9-based device which showed a PCE of 0.7% with a FF of 47%, V OC of 0.62 V and J SC of 2.4 mA cm-2.

Fano interference between collective modes in cuprate high-Tc superconductors.

Cuprate high-Tc superconductors are known for their intertwined interactions and the coexistence of competing orders. Uncovering experimental signatures of these interactions is often the first step in understanding their complex relations. A typical spectroscopic signature of the interaction between a discrete mode and a continuum of excitations is the Fano resonance/interference, characterized by the asymmetric light-scattering amplitude of the discrete mode as a function of the electromagnetic driving frequency. In this study, we report a new type of Fano resonance manifested by the nonlinear terahertz response of cuprate high-Tc superconductors, where we resolve both the amplitude and phase signatures of the Fano resonance. Our extensive hole-doping and magnetic field dependent investigation suggests that the Fano resonance may arise from an interplay between the superconducting fluctuations and the charge density wave fluctuations, prompting future studies to look more closely into their dynamical interactions.

Submaximal cardiopulmonary exercise testing predicts 90-day survival after liver transplantation.

Liver transplantation has a significant early postoperative mortality rate. An accurate preoperative assessment is essential for minimizing mortality and optimizing limited donor organ resources. This study assessed the feasibility of preoperative submaximal cardiopulmonary exercise testing (CPET) for determining the cardiopulmonary reserve in patients being assessed for liver transplantation and its potential for predicting 90-day posttransplant survival. One hundred eighty-two patients underwent CPET as part of their preoperative assessment for elective liver transplantation. The 90-day mortality rate, critical care length of stay, and hospital length of stay were determined during the prospective posttransplant follow-up. One hundred sixty-five of the 182 patients (91%) successfully completed CPET; this was defined as the ability to determine a submaximal exercise parameter: the anaerobic threshold (AT). Sixty of the 182 patients (33%) underwent liver transplantation, and the mortality rate was 10.0% (6/60). The mean AT value was significantly higher for survivors versus nonsurvivors (12.0 ± 2.4 versus 8.4 ± 1.3 mL/minute/kg, P < 0.001). Logistic regression revealed that AT, donor age, blood transfusions, and fresh frozen plasma transfusions were significant univariate predictors of outcomes. In a multivariate analysis, only AT was retained as a significant predictor of mortality. A receiver operating characteristic curve analysis demonstrated sensitivity and specificity of 90.7% and 83.3%, respectively, with good model accuracy (area under the receiver operating characteristic curve = 0.92, 95% confidence interval = 0.82-0.97, P = 0.001). The optimal AT level for survival was defined to be >9.0 mL/minute/kg. The predictive value was improved when the ideal weight was substituted for the actual body weight of a patient with refractory ascites, even after a correction for the donor's age. In conclusion, the preoperative cardiorespiratory reserve (as defined by CPET) is a sensitive and specific predictor of early survival after liver transplantation. The predictive value of CPET requires further evaluation.