Effect of silver electrode wetting state on oxygen reduction electrochemistry.

Surface wettability plays an important role in heterogeneous electrocatalysis. Here we report a facile laser ablation strategy to directly modify the wettability of the silver catalyst surface and investigate its effect on oxygen reduction reaction (ORR). A broad range tuning of 2e-/4e- ORR pathways was achieved, with hydrophilic silver surfaces (contact angle (θw) 31.1°± 0.6°) showing high activity and selectivity towards 4e- reduction of oxygen to water.

Air-Stability and Carrier Type in Conductive M3(Hexaaminobenzene)2, (M = Co, Ni, Cu).

Herein, we investigate the effects of changing the metal ions in the M-HAB system, with HAB = hexaaminobenzene ligands and M = Co, Ni, Cu. The phyiscal characteristics of this MOF family are insensitive to changes in the metal cation, which enables systematic evaluation of the effect of metal cation identity on electrical transport properties. We observe that the metal ion profoundly influences the electrical conductivity and dominant carrier type in the resulting MOF and the air-stability thereof. Cu-HAB and Co-HAB are determined to exhibit n-type conduction under both ambient and nitrogen conditions; Ni-HAB is found to be ambipolar, with its dominant carrier type dramatically affected by the environment. We examine these results through calculation of the band structure, the partial density of states, and charge transfer analysis. Unlike traditional conductive organic materials, we find that the air-stability is not well predicted by the LUMO level of these n-type MOFs but instead is additionally dependent on the occupancy and orientation of the metal ion's d-orbitals and the resulting interaction between the metal ion and ligand. This study provides fundamental insights for rational design of air-stable, electronically conductive MOFs.

MoleculeNet: a benchmark for molecular machine learning.

Molecular machine learning has been maturing rapidly over the last few years. Improved methods and the presence of larger datasets have enabled machine learning algorithms to make increasingly accurate predictions about molecular properties. However, algorithmic progress has been limited due to the lack of a standard benchmark to compare the efficacy of proposed methods; most new algorithms are benchmarked on different datasets making it challenging to gauge the quality of proposed methods. This work introduces MoleculeNet, a large scale benchmark for molecular machine learning. MoleculeNet curates multiple public datasets, establishes metrics for evaluation, and offers high quality open-source implementations of multiple previously proposed molecular featurization and learning algorithms (released as part of the DeepChem open source library). MoleculeNet benchmarks demonstrate that learnable representations are powerful tools for molecular machine learning and broadly offer the best performance. However, this result comes with caveats. Learnable representations still struggle to deal with complex tasks under data scarcity and highly imbalanced classification. For quantum mechanical and biophysical datasets, the use of physics-aware featurizations can be more important than choice of particular learning algorithm.

Retrosynthetic Reaction Prediction Using Neural Sequence-to-Sequence Models.

We describe a fully data driven model that learns to perform a retrosynthetic reaction prediction task, which is treated as a sequence-to-sequence mapping problem. The end-to-end trained model has an encoder-decoder architecture that consists of two recurrent neural networks, which has previously shown great success in solving other sequence-to-sequence prediction tasks such as machine translation. The model is trained on 50,000 experimental reaction examples from the United States patent literature, which span 10 broad reaction types that are commonly used by medicinal chemists. We find that our model performs comparably with a rule-based expert system baseline model, and also overcomes certain limitations associated with rule-based expert systems and with any machine learning approach that contains a rule-based expert system component. Our model provides an important first step toward solving the challenging problem of computational retrosynthetic analysis.

Impact of Diagnostic Delay and Associated Factors on Clinical Outcomes in a U.S. Inflammatory Bowel Disease Cohort.

BACKGROUND: The impact of diagnostic delay in inflammatory bowel disease, including Crohn's disease (CD) and ulcerative colitis (UC), on disease course remains uncertain. This study examines factors that may influence time to diagnosis and disease outcomes in a U.S. patient cohort. METHODS: We retrospectively collected data on patient characteristics, time to diagnosis, disease phenotype, and complications in 177 patients with inflammatory bowel disease (110 CD and 67 UC) diagnosed at our institution from 2008 to 2015. Factors potentially affecting time to diagnosis were analyzed. Association between disease complications (perianal disease, intestinal strictures, surgery, fistula, abscess, and perforation) and time to diagnosis was tested by multivariable analysis. RESULTS: The median time to diagnosis was longer for patients with CD compared with patients with UC (median 9.5 versus 3.1 months; P < 0.001). The median time from symptom onset to initial physician visit was similar for patients with CD and patients with UC (1 month). However, the median time from symptom onset to specialist evaluation was longer for patients with CD compared with patients with UC: 7 months (interquartile range: 3-23) versus 3 months (interquartile range: 1-8), respectively (P < 0.001). In CD, ileal disease and hematochezia were positively and negatively correlated, respectively, with longer time to diagnosis (P < 0.05). Compared with patients with time to diagnosis ≤4 months, patients with time >26 months had increased overall complications (odds ratio, 8.22; P = 0.007) and intestinal strictures (odds ratio, 8.96; P = 0.012) at time of diagnosis. Such correlation persisted at follow-up. CONCLUSIONS: Time to diagnosis was long in CD. Physician-related delay in diagnosing CD was associated with increased overall complications and intestinal strictures (See Video Abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B646).

Building a More Predictive Protein Force Field: A Systematic and Reproducible Route to AMBER-FB15.

The increasing availability of high-quality experimental data and first-principles calculations creates opportunities for developing more accurate empirical force fields for simulation of proteins. We developed the AMBER-FB15 protein force field by building a high-quality quantum chemical data set consisting of comprehensive potential energy scans and employing the ForceBalance software package for parameter optimization. The optimized potential surface allows for more significant thermodynamic fluctuations away from local minima. In validation studies where simulation results are compared to experimental measurements, AMBER-FB15 in combination with the updated TIP3P-FB water model predicts equilibrium properties with equivalent accuracy, and temperature dependent properties with significantly improved accuracy, in comparison with published models. We also discuss the effect of changing the protein force field and water model on the simulation results.

Catalytic upgrading of biomass-derived methyl ketones to liquid transportation fuel precursors by an organocatalytic approach.

A highly efficient water-tolerant, solid-base catalyst for the self-condensation of biomass-derived methyl ketones to jet-diesel fuel precursors was developed by grafting site-isolated secondary amines on silica-alumina supports. It is shown that apart from the nature and density of amine groups and the spatial separation of the acidic and basic sites, the acidity of the support material plays a critical role in defining the catalytic activity. It is also found that a combination of weakly acidic silanol/aluminol with secondary amine groups can mimic proline catalysts and are more effective in catalyzing the selective dimerization reaction than the combination of amines with organic acids. In situ FTIR measurements demonstrate that acidic groups activate methyl ketones through their carbonyl groups leading to a favorable CC bond formation step involving an enamine intermediate. DFT analysis of the reaction pathway confirms that CC bond formation is the rate-limiting step.

The role of hydroxyl group acidity on the activity of silica-supported secondary amines for the self-condensation of n-butanal.

The catalytic activity of secondary amines supported on mesoporous silica for the self-condensation of n-butanal to 2-ethylhexenal can be altered significantly by controlling the Brønsted acidity of M--OH species present on the surface of the support. In this study, M--OH (M=Sn, Zr, Ti, and Al) groups were doped onto the surface of SBA-15, a mesoporous silica, prior to grafting secondary propyl amine groups on to the support surface. The catalytic activity was found to depend critically on the synthesis procedure, the nature and amount of metal species introduced and the spatial separation between the acidic sites and amine groups. DFT analysis of the reaction pathway indicates that, for weak Brønsted acid groups, such as Si--OH, the rate-limiting step is C--C bond formation, whereas for stronger Brønsted acid groups, such as Ti and Al, hydrolysis of iminium species produced upon C--C bond formation is the rate-limiting step. Theoretical analysis shows further that the apparent activation energy decreases with increasing Brønsted acidity of the M--OH groups, consistent with experimental observation.

Subnanometer-sized Pt/Sn alloy cluster catalysts for the dehydrogenation of linear alkanes.

The reaction pathways for the dehydrogenation of ethane, propane, and butane, over Pt are analyzed using density functional theory (DFT). Pt nanoparticles are represented by a tetrahedral Pt4 cluster. The objectives of this work were to establish which step is rate limiting and which one controls the selectivity for forming alkenes as opposed to causing further dehydrogenation of adsorbed alkenes to produce precursors responsible for catalyst deactivation due to coking. Further objectives of this work are to identify the role of adsorbed hydrogen, derived from H2 fed together with the alkane, on the reaction pathway, and the role of replacing one of the four Pt atoms by a Sn atom. A comparison of Gibbs free energies shows that in all cases the rate-determining step is cleavage of a C-H bond upon alkane adsorption. The selectivity to alkene formation versus precursors to coking is dictated by the relative magnitudes of the activation energies for alkene desorption and dehydrogenation of the adsorbed alkene. The presence of an adsorbed H atom on the cluster facilitates alkene desorption relative to dehydrogenation of the adsorbed alkene. Substitution of a Sn atom in the cluster to produce a Pt3Sn cluster leads to a downward shift of the potential energy surface for the reaction and causes an increase of the activity of the catalyst as suggested by recent experiments due to the lower net activation barrier for the rate limiting step. However, the introduction of Sn does not alter the relative activation barriers for gas-phase alkene formation versus loss of hydrogen from the adsorbed alkene, the process leading to the formation of coke precursors.

Ab initio simulations reveal that reaction dynamics strongly affect product selectivity for the cracking of alkanes over H-MFI.

Product selectivity of alkane cracking catalysis in the H-MFI zeolite is investigated using both static and dynamic first-principles quantum mechanics/molecular mechanics simulations. These simulations account for the electrostatic- and shape-selective interactions in the zeolite and provide enthalpic barriers that are closely comparable to experiment. Cracking transition states for n-pentane lead to a metastable intermediate (a local minimum with relatively small barriers to escape to deeper minima) where the proton is shared between two hydrocarbon fragments. The zeolite strongly stabilizes these carbocations compared to the gas phase, and the conversion of this intermediate to more stable species determines the product selectivity. Static reaction pathways on the potential energy surface starting from the metastable intermediate include a variety of possible conversions into more stable products. One-picosecond quasiclassical trajectory simulations performed at 773 K indicate that dynamic paths are substantially more diverse than the potential energy paths. Vibrational motion that is dynamically sampled after the cracking transition state causes spilling of the metastable intermediate into a variety of different products. A nearly 10-fold change in the branching ratio between C2/C3 cracking channels is found upon inclusion of post-transition-state dynamics, relative to static electronic structure calculations. Agreement with experiment is improved by the same factor. Because dynamical effects occur soon after passing through the rate-limiting transition state, it is the dynamics, and not only the potential energy barriers, that determine the catalytic selectivity. This study suggests that selectivity in zeolite catalysis is determined by high temperature pathways that differ significantly from 0 K potential surfaces.

Acute electrical isolation is a necessary but insufficient endpoint for achieving durable PV isolation: the importance of closing the visual gap.

AIMS: Temporary, ablation-mediated effects such as oedema may cause reversible pulmonary vein (PV) isolation. To investigate this, point-by-point circumferential ablation was performed to achieve acute electrical PV isolation with an incomplete circumferential ablation line. Then, the impact of this intentional 'visual gap' (ViG) on the conduction properties of the ablation lesion set was assessed with adenosine and pacing manoeuvres. METHODS AND RESULTS: Twenty-eight patients undergoing ablation for paroxysmal (n= 20) or persistent atrial fibrillation (n= 8) were included. Pulmonary vein (PV) ablation was performed around ipsilateral vein pairs. Once acute isolation was achieved, ablation was halted and the presence and size of the ViG were calculated. The ViG electrophysiological properties were tested with pace capture along the ViG at 10 mA/2 ms, and assessment for dormant PV conduction with adenosine. Despite electrical isolation, a ViG was present in 75% (n= 42/56) of vein pairs (21 of 28 left PVs and 21 of 28 right PVs). There was no difference in the ViG size between the left and right PVs (22.1 ± 14.2 and 17.3 ± 11.3 mm, P > 0.05). Dormant PV connections were revealed by adenosine in more than a quarter (n= 12/42) of acutely isolated PV pairs, of which the majority were dependent on conduction through the ViG. CONCLUSIONS: Electrical PV isolation can usually be achieved without complete circumferential ablation. However, more than a quarter of these 'isolated' PVs exhibit dormant conduction-predominantly via the un-ablated 'ViGs' in the ablation lesion set. These findings support the hypothesis that reversible tissue injury contributes to PV isolation that may be acute but not necessarily durable.

Retrospective drug utilization review: impact of pharmacist interventions on physician prescribing.

OBJECTIVES: To evaluate the impact of retrospective drug utilization review (RDUR), pharmacist's interventions on physician prescribing, and the level of spillover effect on future prescriptions following the intervention. METHODS: A retrospective case-control study was conducted at a pharmacy benefits management company using the available prescription data from April 2004 to August 2005. RDUR conflicts evaluated and intervened by a clinical pharmacist served as a case group, whereas conflicts that were not evaluated and intervened by a clinical pharmacist served as a control group. RESULTS: A total of 40,284 conflicts in cases and 13,044 in controls were identified. For cases, 32,780 interventions were considered nonrepetitive, and 529 were repetitive. There were 22,870 physicians in cases that received intervention letters and 2348 physicians in the control group that would have received intervention letters during the study period. Each physician received on average 1.4 interventions for cases vs 3.0 for controls. Among the case physicians who were intervened during the study period, 2.2% (505) were involved in a repeated intervention vs 18.2% (428) in controls (P < 0.001), which is an eight-fold difference. The most common conflict intervened on in cases was therapeutic appropriateness (8277, 25.3%), and for controls it was drug-drug interactions (1796, 25.4%). The overall interventional spillover effect in cases was 98.4% vs 89.4% in controls (P = 0.01). CONCLUSION: RDUR is an effective interventional program which results in decreased numbers of interventions per physician and provides a significant impact on future prescribing habits.

Impact of implantable cardioverter-defibrillator recalls on patients' anxiety, depression, and quality of life.

BACKGROUND: In the past 2 years, multiple implantable cardioverter-defibrillator (ICD) manufacturers have issued recalls on ICD models due to the potential for serious malfunction and even patient death. Previous studies examining the relationship between these recalls and patients' psychological well-being have been limited by small sample size and conflicting results. The purpose of this study is to examine the association between ICD recalls and patients' anxiety, depression, and quality of life. METHODS: Patients were drawn from an outpatient electrophysiology clinic at a tertiary care hospital in New York City. Patients who had devices subject to a recall (cases) were identified from lists provided by device manufacturer and controls (patients with ICDs not subjected to a recall) were drawn from a convenience sample of outpatients. The survey instrument consisted of two validated questionnaires--Hospital Anxiety and Depression Score (HADS) and MacNew heart disease health-related quality of life (QOL) instrument. In addition, a series of Likert-type scales were designed to elucidate patients' concerns related to the following domains: anger, trust, hope, concerns regarding ICD shock, fear of death (FOD), and physicians' ability to reduce their concern about the ICD recall. Data were analyzed using simple descriptive statistics and bivariate analyses (chi(2) and t-test) as appropriate. RESULT: Sixty-one cases and 43 control patients were enrolled. Thirty-two patients (52%) with devices subject to a recall opted for a generator replacement. There were no significant differences in the mean scores on the HADS scale, or the MacNew QOL scale between these two groups of patients (cases and controls). Subgroup analysis within the group of patients whose ICDs were recalled (cases) revealed a reduced QOL among patients with a class I recall (reasonable probability that the product will cause serious adverse health consequences or death) as compared to those with a class II recall (product may cause temporary or medically reversible adverse health consequences) (P = 0.01). Both cases and control patients reported having reduced trust in the health-care system. On the whole, however, patients were satisfied with the way their physicians dealt with the recall. There was no significant change in the overall concern of ICD shocks or FOD between the two groups. CONCLUSION: In this study of ICD recall, we found no difference in the levels of anxiety, depression, or QOL expressed by patients with an ICD subject to a recall as compared to those without. These findings may be a reflection of good physician-patient communication, which might have reduced any anxiety associated with recalls.

Impact of drug use and comorbidities on in-hospital falls in patients with chronic kidney disease.

BACKGROUND: In-hospital falls are a major problem in healthcare institutions and contribute to morbidity and mortality in this setting. Patients with chronic kidney disease (CKD) were previously found to be at higher risk for experiencing an in-hospital fall. OBJECTIVE: To evaluate the association between comorbidities and drug use with the risk of in-hospital falls in adults with CKD. METHODS: A retrospective case-control study was conducted in patients with CKD hospitalized between January 1, 1998, and June 30, 2003. Cases included patients who experienced an in-hospital fall, were 18 years of age or older, and had been hospitalized for more than 24 hours. For every case, 2 controls were identified and matched for CKD, age, and sex. Information about comorbidities and drug use was collected from an electronic medical data repository. Statistical tests performed were t-tests, chi2 analysis, and multivariate logistic regression, using occurrence of a fall as the dependent variable and race, comorbidities, and drug groups as covariates. RESULTS: There were 635 fall cases that met study criteria. The mean age of patients was 68 +/- 15 years, 54% were female, and 82% were white. There were 1270 matched controls with CKD who were included in the regression analysis. Comorbidities that increased the likelihood of experiencing an in-hospital fall were dementia (OR 2.63), pneumonia (OR 1.72), gastrointestinal disease (OR 1.41), and diabetes (OR 1.31). Drugs associated with an in-hospital fall were antidepressants (OR 1.65) and anticonvulsants (OR 1.52). CONCLUSIONS: Several comorbidities, especially dementia, significantly increase the risk of experiencing an in-hospital fall in patients with CKD. Drugs that place CKD patients at risk include antidepressants and anticonvulsants.

Comparative safety and immunogenicity of two attenuated enterotoxigenic Escherichia coli vaccine strains in healthy adults.

A vaccine against enterotoxigenic Escherichia coli (ETEC) is needed to prevent diarrheal illness among children in developing countries and at-risk travelers. Two live attenuated ETEC strains, PTL002 and PTL003, which express the ETEC colonization factor CFA/II, were evaluated for safety and immunogenicity. In a randomized, double-blind, placebo-controlled trial, 19 subjects ingested one dose, and 21 subjects ingested two doses (days 0 and 10) of PTL-002 or PTL-003 at 2 x 10(9) CFU/dose. Anti-CFA/II mucosal immune responses were determined from the number of antibody-secreting cells (ASC) in blood measured by enzyme-linked immunospot assay, the antibody in lymphocyte supernatants (ALS) measured by enzyme-linked immunosorbent assay (ELISA), and fecal immunoglobulin A (IgA) levels determined by ELISA. Time-resolved fluorescence (TRF) ELISA was more sensitive than standard colorimetric ELISA for measuring serum antibody responses to CFA/II and its components, CS1 and CS3. Both constructs were well tolerated. Mild diarrhea occurred after 2 of 31 doses (6%) of PTL-003. PTL-003 produced more sustained intestinal colonization than PTL-002 and better IgA response rates: 90% versus 55% (P = 0.01) for anti-CFA/II IgA-ASCs, 55% versus 30% (P = 0.11) for serum anti-CS1 IgA by TRF, and 65% versus 25% (P = 0.03) for serum anti-CS3 IgA by TRF. Serum IgG response rates to CS1 or CS3 were 55% in PTL-003 recipients and 15% in PTL-002 recipients (P = 0.02). Two doses of either strain were not significantly more immunogenic than one. Based on its superior immunogenicity, which was comparable to that of a virulent ETEC strain and other ETEC vaccine candidates, PTL-003 will be developed further as a component of a live, oral attenuated ETEC vaccine.

Ventricular arrhythmia: role of the implantable cardioverter defibrillator and radiofrequency ablation in addition to drugs.

The control of life-threatening arrhythmias in the prevention of sudden cardiac death has been a long-standing challenge to clinicians. Large-scale, randomized, controlled trials have contributed immensely to our understanding of the management of life-threatening arrhythmias. There are many causes of life-threatening ventricular arrhythmias, which they occur mostly in the setting of healed myocardial infarction. Available treatments for the management of ventricular arrhythmias include antiarrhythmic drugs, implantable cardioverter defibrillators and catheter ablation. Each therapy provides unique advantages for selected patients with life-threatening arrhythmias. Because the goal of arrhythmia management is not only to provide the single best therapy but to provide the greatest assurance of symptomatic arrhythmia control, the use of combined therapy has become a standard treatment strategy for patients with sustained ventricular arrhythmias. This review will discuss the different modes of treatment available for the treatment of life-threatening ventricular arrhythmias, and their potential risks and benefits. The rationale for using hybrid or combination therapy will be presented. Finally, some of the better-known primary and secondary prevention trials for treatment of ventricular tachycardias will be reviewed.