The rational design of well-defined, first-row transition metal complexes that can activate dioxygen has been a challenging goal for the synthetic inorganic chemist. The activation of O2 is important ...in part because of its central role in the functioning of metalloenzymes, which utilize O2 to perform a number of challenging reactions including the highly selective oxidation of various substrates. There is also great interest in utilizing O2, an abundant and environmentally benign oxidant, in synthetic catalytic oxidation systems. This Perspective brings together recent examples of biomimetic Fe and Mn complexes that can activate O2 in heme or nonheme-type ligand environments. The use of oxidants such as hypervalent iodine (e.g., ArIO), peracids (e.g., m-CPBA), peroxides (e.g., H2O2) or even superoxide is a popular choice for accessing well-characterized metal–superoxo, metal–peroxo, or metal–oxo species, but the instances of biomimetic Fe/Mn complexes that react with dioxygen to yield such observable metal–oxygen species are surprisingly few. This Perspective focuses on mononuclear Fe and Mn complexes that exhibit reactivity with O2 and lead to spectroscopically observable metal–oxygen species, and/or oxidize biologically relevant substrates. Analysis of these examples reveals that solvent, spin state, redox potential, external co-reductants, and ligand architecture can all play important roles in the O2 activation process.
Nearly all studies of gastric adenocarcinoma in the United States have relied on national cancer databases, which do not include data on Helicobacter pylori infection, the most well-known risk factor ...for gastric cancer. We collected data from a large cohort of patients in the United States to calculate the incidence of and risk factors for nonproximal gastric adenocarcinomas after detection of H pylori. Secondary aims included identifying how treatment and eradication affect cancer risk.
We performed a retrospective cohort study, collecting data from the Veterans Health Administration on 371,813 patients (median age 62 years; 92.3% male) who received a diagnosis of H pylori infection from January 1, 1994, through December 31, 2018. The primary outcome was a diagnosis of distal gastric adenocarcinoma 30 days or more after detection of H pylori infection. We performed a time to event with competing risk analysis (with death before cancer as a competing risk).
The cumulative incidence of cancer at 5, 10, and 20 years after detection of H pylori infection was 0.37%, 0.5%, and 0.65%, respectively. Factors associated with cancer included older age at time of detection of H pylori infection (subhazard ratio SHR, 1.13; 95% confidence interval CI, 1.11–1.15; P < .001), black/African American race (SHR, 2.00; 95% CI, 1.80–2.22), Asian race (SHR, 2.52; 95% CI, 1.64–3.89) (P < .001 for race), Hispanic or Latino ethnicity (SHR, 1.59; 95% CI, 1.34–1.87; P < .001), and history of smoking (SHR, 1.38; 95% CI, 1.25–1.52; P < .001). Women had decreased risk of gastric adenocarcinoma compared with men (SHR, 0.52; 95% CI, 0.40–0.68; P < .001); patients whose H pylori infection was detected based on serum antibody positivity also had a reduced risk of cancer (SHR 0.74; 95% CI, 0.54–1.04; P = .04). Patients who received treatment for their H pylori infection still had an increased risk of gastric cancer (SHR, 1.16; 95% CI, 0.74–1.83; P = .51) but confirmed H pylori eradication after treatment reduced risk of gastric cancer (SHR, 0.24; 95% CI, 0.15–0.41; P < .001).
In a study of 371,813 veterans with a diagnosis of H pylori infection, we found significantly higher risks of gastric cancer in racial and ethnic minorities and smokers. Treatment of H pylori infection decreased risk only if eradication was successful. Studies are needed on the effects of screening high-risk persons and to identify quality measures for diagnosis, resistance patterns, and treatment efficacy.
Heme proteins utilize the heme cofactor, an iron porphyrin, to perform a diverse range of reactions including dioxygen binding and transport, electron transfer, and oxidation/oxygenations. These ...reactions share several key metalloporphyrin intermediates, typically derived from dioxygen and its congeners such as hydrogen peroxide. These species are composed of metal–dioxygen, metal–superoxo, metal–peroxo, and metal–oxo adducts. A wide variety of synthetic metalloporphyrinoid complexes have been synthesized to generate and stabilize these intermediates. These complexes have been studied to determine the spectroscopic features, structures, and reactivities of such species in controlled and well-defined environments. In this Review, we summarize recent findings on the reactivity of these species with common porphyrinoid scaffolds employed for biomimetic studies. The proposed mechanisms of action are emphasized. This Review is organized by structural type of metal–oxygen intermediate and broken into subsections based on the metal (manganese and iron) and porphyrinoid ligand (porphyrin, corrole, and corrolazine).
The term acute‐on‐chronic liver failure (ACLF) is intended to identify patients with chronic liver disease who develop rapid deterioration of liver function and high short‐term mortality after an ...acute insult. The two prominent definitions (European Association for the Study of the Liver EASL and Asian Pacific Association for the Study of the Liver APASL) differ, and existing literature applies to narrow patient groups. We sought to compare ACLF incidence and mortality among a diverse cohort of patients with compensated cirrhosis, using both definitions. This was a retrospective cohort study of patients with incident compensated cirrhosis in the Veterans Health Administration from 2008 to 2016. First ACLF events were identified for each definition. Incidence rates were computed as events per 1,000 person‐years, and mortality was calculated at 28 and 90 days. Among 80,383 patients with cirrhosis with 3.35 years median follow‐up, 783 developed EASL and APASL ACLF, 4,296 developed EASL ACLF alone, and 574 developed APASL ACLF alone. The incidence rate of APASL ACLF was 5.7 per 1,000 person‐years (95% confidence interval CI: 5.4‐6.0), and the incidence rate of EASL ACLF was 20.1 (95% CI: 19.5‐20.6). The 28‐day and 90‐day mortalities for APASL ACLF were 41.9% and 56.1%, respectively, and were 37.6% and 50.4% for EASL ACLF. The median bilirubin level at diagnosis of EASL‐alone ACLF was 2.0 mg/dL (interquartile range: 1.1‐4.0). Patients with hepatitis C or nonalcoholic fatty liver disease had among the lowest ACLF incidence rates but had the highest short‐term mortality. Conclusion: There is significant discordance in ACLF events by EASL and APASL criteria. The majority of patients with EASL‐alone ACLF have preserved liver function, suggesting the need for more liver‐specific ACLF criteria.
Dual-sourcing inventory systems, in which one supplier is faster (i.e., express) and more costly, while the other is slower (i.e., regular) and cheaper, arise naturally in many real-world supply ...chains. These systems are notoriously difficult to optimize because of the complex structure of the optimal solution and the curse of dimensionality, having resisted solution for over 40 years. Recently, so-called tailored base-surge (TBS) policies have been proposed as a heuristic for the dual-sourcing problem. Under such a policy, a constant order is placed at the regular source in each period, while the order placed at the express source follows a simple order-up-to rule. Numerical experiments by several authors have suggested that such policies perform well as the lead time difference between the two sources grows large, which is exactly the setting in which the curse of dimensionality leads to the problem becoming intractable. However, providing a theoretical foundation for this phenomenon has remained a major open problem. In this paper, we provide such a theoretical foundation by proving that a simple TBS policy is indeed asymptotically optimal as the lead time of the regular source grows large, with the lead time of the express source held fixed. Our main proof technique combines novel convexity and lower-bounding arguments, an explicit implementation of the vanishing discount factor approach to analyzing infinite-horizon Markov decision processes, and ideas from the theory of random walks and queues, significantly extending the methodology and applicability of a novel framework for analyzing inventory models with large lead times recently introduced by Goldberg and coauthors in the context of lost-sales models with positive lead times.
This paper was accepted by Gad Allon, operations management.
•Accident narratives are studied for automatic coding with machine learning.•Body part(s), source, event, hospitalization, and amputation are considered.•Word embeddings approaches are utilized to ...classify accident narratives.•BERT word embeddings outperform competing approaches.•Trained models generalize well in two transfer learning contexts.
Introduction: Ensuring occupational health and safety is an enormous concern for organizations, as accidents not only harm workers but also result in financial losses. Analysis of accident data has the potential to reveal insights that may improve capabilities to mitigate future accidents. However, because accident data are often transcribed textually, analyzing these narratives proves difficult. This study contributes to a recent stream of literature utilizing machine learning to automatically label accident narratives, converting them into more easily analyzable fields. Method: First, a large dataset of accident narratives in which workers were injured is collected from the U.S. Occupational Safety and Health Administration (OSHA). Word embeddings-based text mining is implemented; compared to past works, this methodology offers excellent performance. Second, to improve the richness of analyses, each record is assessed across five dimensions. The machine learning models provide classifications of body part(s) injured, the source of the injury, the type of event causing the injury, whether a hospitalization occurred, and whether an amputation occurred. Finally, demonstrating generalizability, the trained models are deployed to analyze two additional datasets of accident narratives in the construction industry and the mining and metals industry (transfer learning). Practical Applications: These contributions improve organizations’ capacities to rapidly analyze textual accident narratives.
Conspectus There has been considerable interest in hydrogen atom transfer (HAT) reactions mediated by metal/oxygen species because of their central role in metalloenzyme function as well as synthetic ...catalysts. This Account focuses on our progress in synthesizing high-valent metal–oxo and metal–hydroxo porphyrinoid complexes and determining their reactivities in a range of HAT processes. For these studies we have utilized corrolazine and corrole ligands, which are a ring-contracted subclass of porphyrinoid compounds designed to stabilize high-valent metal complexes. The high-valent manganese complex MnV(O)(TBP8Cz) (TBP8Cz = octakis(4-tert-butylphenyl)corrolazine3−) provided an early example of a well-characterized low-potential oxidant that can still be effective at abstracting H atoms from certain C–H/O–H bonds. Approximating the thermodynamics of the HAT reactivity of the MnV(O) complex and related species with the help of a square scheme approach, in which HAT can be formally separated into proton (pK a) and electron transfers ( E°), indicates that affinity for the proton (i.e., the basicity) is a key factor in promoting HAT. Anionic axial ligands have a profound influence on the HAT reactivity of MnV(O)(TBP8Cz), supporting the conclusion that basicity is a critical parameter in determining the reactivity. The influence of Lewis acids on MnV(O)(TBP8Cz) was examined, and it was shown that both the electronic structure and reactivity toward HAT were significantly altered. High-valent Cr(O), Re(O), and Fe(O) corrolazines were prepared, and a range of HAT reactions were studied with these complexes. The chromium and manganese complexes form a rare pair of structurally characterized CrV(O) and MnV(O) species in identical ligand environments, allowing for a direct comparison of their HAT reactivities. Although the CrV(O) species was the better oxidant as measured by redox potentials, the MnV(O) species was significantly more reactive in HAT oxidations, pointing again to basicity as a key determinant of HAT reactivity. The iron complex, FeIV(O)(TBP8Cz+•), is an analogue of the heme enzyme Compound I intermediate, and was found to be mildly reactive toward H atom abstraction from C–H bonds. In contrast, ReV(O)(TBP8Cz) was inert toward HAT, although one-electron oxidation to ReV(O)(TBP8Cz+•) led to some interesting reactivity mediated by the π-radical-cation ligand alone. Other ligand modifications, including peripheral substitution as well as novel alkylation of the meso position on the Cz core, were examined for their influence on HAT. A highly sterically encumbered corrole, tris(2,4,6-triphenylphenyl)corrole (ttppc), was employed for the isolation and structural characterization of the first MnIV(OH) complex in a porphyrinoid environment, MnIV(OH)(ttppc). This complex was highly reactive in HAT with O–H substrates and was found to be much more reactive than its higher-oxidation-state counterpart MnV(O)(ttppc), providing important mechanistic insights. These studies provided fundamental knowledge on the relationship between structure and function in high-valent M(O) and M(OH) models of heme enzyme reactivity.
•Sufficient conditions for weak and strong time consistency.•The multistage-static problem can fail to be weakly time consistent•The multistage-static problem can be weakly but not strongly time ...consistent•The multistage-static problem can have no optimal base-stock policy.•It is strongly time consistent but the two formulations have different optimal values.
Recently, there has been a growing interest in developing inventory control policies which are robust to model misspecification. One approach is to posit that nature selects a worst-case distribution for any relevant stochastic primitives from some pre-specified family. Several communities have observed that a subtle phenomena known as time inconsistency can arise in this framework. In particular, it becomes possible that a policy which is optimal at time zero may not be optimal for the associated optimization problem in which the decision-maker recomputes her policy at each point in time, which has implications for implementability. If there exists a policy which is optimal for both formulations, we say that the policy is time consistent, and the problem is weakly time consistent. If every optimal policy is time consistent, we say that the problem is strongly time consistent. We study these phenomena in the context of managing an inventory over time, when only the mean, variance, and support are known for the demand at each stage. We provide several illustrative examples showing that here the question of time consistency can be quite subtle. We complement these observations by providing simple sufficient conditions for weak and strong time consistency. Although a similar phenomena was previously identified by Shapiro for the setting in which only the mean and support of the demand are known, here our model is rich enough to exhibit a variety of additional interesting behaviors.
The coronavirus disease of 2019 (COVID-19) pandemic has necessitated a transition to online courses, prompting widespread consequences for higher education. Ensuring academic integrity poses a ...serious concern in these circumstances. Drawn from my experiences teaching online programming courses, I discuss the considerable and manifold flaws in our current anti-cheating measures. I propose a series of strategies that instructors can pursue to make assessments more resilient to cheating. Although there is no panacea, we must begin by acknowledging the problem facing us and discussing earnestly how we can refortify academic integrity.
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