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The interfacial electron transfer events that underpin electrochemistry effect one-electron oxidation or reduction of substrates. In contrast, selective bond-forming and -breaking in synthetic chemistry requires the choreographed management of two-electron steps. Thus, application of electrochemistry in synthesis requires strategies to aggregate multiple redox equivalents to engender multi-electron reactions. Here we demonstrate that sequential disproportionation reactions can enable selective aggregation of two- or four electron-holes at a hypervalent iodine center. Disproportionation of an anodically generated iodanyl radical (i.e., I(II) species) affords an iodosylbenzene derivative (i.e., I(III) species). Subsequent iodosylbenzene disproportionation can be triggered to provide access to iodoxybenzene (i.e., I(V) species). Both the transient iodanyl radical intermediate that engages in disproportionation to afford I(III) species and the O-bridged bis-I(III) compound that mediates iodosylbenzene disproportionation to afford I(V) species have been directly characterized. These results represent the first example of iodanyl radical disproportionation as a means to access I(III) compounds and demonstrate aggregation of four electron at the one-electron potential by selective and sequential disproportionation chemistry.

Background Breast cancer survivors are at increased risk for developing second primary cancers compared with the general population. Little is known about whether body mass index (BMI) increases this risk. We examined the association between BMI and second cancers among women with incident invasive breast cancer. Methods This retrospective cohort included 6481 patients from Kaiser Permanente Colorado and Washington of whom 822 (12.7%) developed a second cancer (mean follow-up was 88.0 months). BMI at the first cancer was extracted from the medical record. Outcomes included: 1) all second cancers, 2) obesity-related second cancers, 3) any second breast cancer, and 4) estrogen receptor–positive second breast cancers. Multivariable Poisson regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for second cancers associated with BMI adjusted for site, diagnosis year, treatment, demographic, and tumor characteristics. Results The mean age at initial breast cancer diagnosis was 61.2 (SD = 11.8) years. Most cases were overweight (33.4%) or obese (33.8%) and diagnosed at stage I (62.0%). In multivariable models, for every 5 kg/m2 increase in BMI, the risk of any second cancer diagnosis increased by 7% (RR = 1.07, 95% CI = 1.01 to 1.14); 13% (RR = 1.13, 95% CI = 1.05 to 1.21) for obesity-related cancers, 11% (RR = 1.11, 95% CI = 1.02 to 1.21) for a second breast cancer, and 15% (RR = 1.15, 95% CI = 1.04 to 1.27) for a second estrogen receptor–positive breast cancer. Conclusions We observed a statistically significant increased risk of second cancers associated with increasing BMI. These findings have important public health implications given the prevalence of overweight and obesity in breast cancer survivors and underscore the need for effective prevention strategies.

Small molecule redox mediators convey interfacial electron transfer events into bulk solution and can enable diverse substrate activation mechanisms in synthetic electrocatalysis. Here we report that 1,2-diiodo-4,5-dimethoxybenzene (1a) is an efficient electrocatalyst for C-H/E-H coupling that operates at as low as 0.5 mol% catalyst loading. Spectroscopic, crystallographic, and computational results indicate a critical role for a three-electron I-I bonding interaction in stabilizing an iodanyl radical intermediate (i.e., formally I(II) species). As a result, 1a operates at more than 100 mV lower potential than related monoiodide catalysts, which results in improved product yield, higher Faradaic efficiency, and expanded substrate scope. The isolated iodanyl radical is chemically competent in C-N bond formation. These results represent the first examples of substrate functionalization at a well-defined I(II) derivative and bona fide iodanyl radical ca-talysis and demonstrate one-electron pathways as a mechanistic alternative to canonical two-electron hypervalent iodine mechanisms. The observation establishes I-I redox cooperation as a new design concept for the development of metal-free redox mediators.

C-H amination reactions provide the opportunity to streamline the synthesis of nitrogen-containing organic small molecules. The impact of intermolecular C-H amination methods, however, is currently limited the frequent requirement for the amine precursors to bear activating groups, such as N-sulfonyl substituents, that are both challenging to remove and not useful synthetic handles for subsequent derivatization. Here, we introduce traceless nitrogen activation for C-H amination-which enables application of selective C-H amination chemistry to the preparation of diverse N-functionalized products-via sequential benzylic C-H N-aminopyridylation followed by Ni-catalyzed C-N cross-coupling with aryl boronic acids. Unlike many C-H amination reactions that provide access to protected amines, the current method installs an easily diversifiable synthetic handle that serves as a lynchpin for C-H amination, deaminative N-N functionalization sequences.

C–H amination chemistry promises to streamline access to nitrogen-containing fine chemicals. The typical need for N-activating substituents — such of N-sulfonyl groups, which are challenging to remove and difficult to engage in synthetic elaboration — limits synthetic utility. Here, we demonstrate that N-benzylaminopyridinium species, generated by C–H aminopyridylation, provide a platform for synthetic elaboration via reductive N–N bond activation to unveil electrophilic N-centered radicals. These reactive intermediates can be trapped either via anti-Markovnikov olefin carboamination to provide access to tetrahydroisoquinolines, which are important heterocycles in molecular therapeutics, or via aza-Rubottom chemistry with silyl enol ethers to provide alpha-amino ketones. This approach broadens the synthetic utility of N-alkylaminopyridinium intermediates and demonstrates a new approach to C–H amination with synthetically addressable, bifunctional reagents.

We measured the frequency of clinicians' assessments for access to lethal means, including firearms and medications in patients at risk of suicide from electronic medical and mental health records in outpatient and emergency settings.We included adult patients who reported suicide ideation on the PHQ-9 depression screener in behavioral health and primary care outpatient settings of a large integrated health system in the U.S. and those with suicidal behavior treated in the emergency department. Two separate natural language processing queries were developed on medical record text documentation: (1) assessment for access to firearms (8,994 patients), (2) assessment for access to medications (4,939 patients).Only 35% of patients had documentation of firearm or medication assessment in the month following treatment for suicidal behavior in the emergency setting. Among those reporting suicidal ideation in outpatient setting, 31% had documentation of firearm assessment and 23% for medication assessment. The accuracy of the estimates was very good for firearm assessment (F1 = 89%) and medication assessment in the outpatient setting (F1 = 91%) and fair for medication assessment in the emergency setting (F1 = 70%) due to more varied documentation styles.Lethal means assessment following report of suicidal ideation or behavior is low in a nonacademic health care setting. Until health systems implement more structured documentation to measure lethal means assessment, such as discrete data field, NLP methods may be used to conduct research and surveillance of this important prevention practice in real-world settings.

BACKGROUND: Both hyperkalemia and hypokalemia can lead to cardiac arrhythmias and are associated with increased mortality. Information on the predictors of potassium in individuals with diabetes in routine clinical practice is lacking. OBJECTIVE: To identify predictors of hyperkalemia and hypokalemia in adults with diabetes. DESIGN: Retrospective cohort study, with classification and regression tree (CART) analysis. PARTICIPANTS: 321,856 individuals with diabetes enrolled in four large integrated health care systems from 2012 to 2013. MAIN MEASURES: We used a single serum potassium result collected in 2012 or 2013. Hyperkalemia was defined as a serum potassium ≥ 5.5 mEq/L and hypokalemia as

Introduction Our primary purpose is to understand comorbidities and health outcomes associated with electronic nicotine delivery systems (ENDS) use. Methods Study participants were Kaiser Permanente (KP) members from eight US regions who joined the Kaiser Permanente Research Bank (KPRB) from September 2015 through December 2019 and completed a questionnaire assessing demographic and behavioral factors, including ENDS and traditional cigarette use. Medical history and health outcomes were obtained from electronic health records. We used multinomial logistic regression to estimate odd ratios (ORs) and 95% confidence intervals (CIs) of current and former ENDS use according to member characteristics, behavioral factors, and clinical history. We used Cox regression to estimate hazard ratios (HRs) and 95% CIs comparing risk of health outcomes according to ENDS use. Results Of 119 593 participants, 1594 (1%) reported current ENDS use and 5603 (5%) reported past ENDS use. ENDS users were more likely to be younger, male, gay or lesbian, and American Indian / Alaskan Native or Asian. After adjustment for confounding, current ENDS use was associated with current traditional cigarette use (OR = 39.55; CI:33.44-46.77), current marijuana use (OR = 6.72; CI:5.61-8.05), history of lung cancer (OR = 2.64; CI:1.42-4.92), non-stroke cerebral vascular disease (OR = 1.55; CI:1.21-1.99), and chronic obstructive pulmonary disease (OR = 2.16; CI:1.77-2.63). Current ENDS use was also associated with increased risk of emergency room (ER) visits (HR = 1.17; CI: 1.05-1.30) and death (HR = 1.84; CI:1.02-3.32). Conclusions Concurrent traditional cigarette use, marijuana use, and comorbidities were prevalent among those who used ENDS, and current ENDS use was associated with an increased risk of ER visits and death. Additional research focused on health risks associated with concurrent ENDS and traditional cigarette use in those with underlying comorbidities is needed.

PHP has an extensive range of functions designed to work with images. You’ve already met one of them, getimagesize(), in Chapter 4. As well as providing useful information about an image’s dimensions, PHP can manipulate images by resizing or rotating them. It can also add text dynamically without affecting the original; it can even create images on the fly.