Efficacy of a Smoking Cessation Intervention for Survivors of Cervical Intraepithelial Neoplasia or Cervical Cancer: A Randomized Controlled Trial.

PURPOSE: Women who smoke and have a history of cervical intraepithelial neoplasia (CIN) or cervical cancer represent a vulnerable subgroup at elevated risk for recurrence, poorer cancer treatment outcomes, and decreased quality of life. The purpose of this study was to evaluate the long-term efficacy of Motivation And Problem Solving (MAPS), a novel treatment well-suited to meeting the smoking cessation needs of this population. METHODS: Women who were with a history of CIN or cervical cancer, age 18 years and older, spoke English or Spanish, and reported current smoking (≥100 lifetime cigarettes plus any smoking in the past 30 days) were eligible. Participants (N = 202) were recruited in clinic in Oklahoma City and online nationally and randomly assigned to (1) standard treatment (ST) or (2) MAPS. ST consisted of repeated referrals to a tobacco cessation quitline, self-help materials, and combination nicotine replacement therapy (patch plus lozenge). MAPS comprised all ST components plus up to six proactive telephone counseling sessions over 12 months. Logistic regression and generalized estimating equations evaluated the intervention. The primary outcome was self-reported 7-day point prevalence abstinence from tobacco at 18 months, with abstinence at 3, 6, and 12 months and biochemically confirmed abstinence as secondary outcomes. RESULTS: There was no significant effect for MAPS over ST at 18 months (14.2% v 12.9%, P = .79). However, there was a significant condition × assessment interaction (P = .015). Follow-up analyses found that MAPS (v ST) abstinence rates were significantly greater at 12 months (26.4% v 11.9%, P = .017; estimated OR, 2.60; 95% CI, 1.19 to 5.89). CONCLUSION: MAPS led to a greater than two-fold increase in smoking abstinence among survivors of CIN and cervical cancer at 12 months. At 18 months, abstinence in MAPS declined to match the control condition and the treatment effect was no longer significant.

Ask-Advise-Connect: Differential Enrollment and Smoking Cessation Outcomes Between Primary Care Patients Who Received Quitline-Delivered Treatment in Spanish vs English.

PURPOSE: This study examined differences in Quitline treatment enrollment, engagement, and smoking cessation outcomes among primary care patients preferring Spanish and English using the evidence-based tobacco treatment Ask-Advise-Connect. METHODS: Ask-Advise-Connect was implemented April 2013 through February 2016 in a large safety-net health system to connect smokers with treatment via a link in the electronic health record. Rates of treatment enrollment, engagement, acceptance of nicotine replacement therapy, and smoking abstinence (self-reported and biochemically confirmed) were compared at 6 months among patients who received treatment in Spanish and English using χ 2 tests. Logistic regression examined language and nicotine replacement therapy and their interaction as predictors of abstinence. RESULTS: The smoking status of 218,915 patients was assessed and recorded in the electronic health record. Smoking prevalence was 8.4% among patients preferring Spanish and 27.0% among those preferring English. Spanish-preferring patients were less likely to enroll in treatment (10.7% vs 12.0%, χ 2 = 12.06, P = .001) yet completed more counseling calls when enrolled (median = 2 vs 1, P <.001). Patients who received treatment in Spanish (vs English) were twice as likely to be abstinent at 6 months (self-reported: 25.1% vs 14.5%, odds ratio [OR] = 1.98, 95% CI, 1.62-2.40; biochemically confirmed: 7.6% vs 3.7%, OR = 2.13, 95% CI, 1.52-2.97). Receipt of nicotine replacement therapy increased abstinence for all patients and language did not interact with nicotine replacement therapy to predict abstinence. CONCLUSIONS: Automated point-of-care approaches such as Ask-Advise-Connect have great potential to reach Spanish-preferring smokers. Those who received tobacco treatment in Spanish (vs English) demonstrated better engagement and cessation outcomes.

Translating the biology of ß common receptor-engaging cytokines into clinical medicine.

The family of cytokines that comprises IL-3, IL-5, and GM-CSF was discovered over 30 years ago, and their biological activities and resulting impact in clinical medicine has continued to expand ever since. Originally identified as bone marrow growth factors capable of acting on hemopoietic progenitor cells to induce their proliferation and differentiation into mature blood cells, these cytokines are also recognized as key mediators of inflammation and the pathobiology of diverse immunologic diseases. This increased understanding of the functional repertoire of IL-3, IL-5, and GM-CSF has led to an explosion of interest in modulating their functions for clinical management. Key to the successful clinical translation of this knowledge is the recognition that these cytokines act by engaging distinct dimeric receptors and that they share a common signaling subunit called ß-common or ßc. The structural determination of how IL-3, IL-5, and GM-CSF interact with their receptors and linking this to their differential biological functions on effector cells has unveiled new paradigms of cell signaling. This knowledge has paved the way for novel mAbs and other molecules as selective or pan inhibitors for use in different clinical settings.

IL-1 Receptor-1 on Vglut2 + neurons in the hippocampus is critical for neuronal and behavioral sensitization after repeated social stress.

Myriad findings connect stress and inflammation to mood disorders. Social defeat in mice promotes the convergence of neuronal, central inflammatory (microglia), and peripheral immune (monocytes) pathways causing anxiety, social avoidance, and "stress-sensitization." Stress-sensitization results in augmented inflammation and the recurrence of anxiety after re-exposure to social stress. Different cell compartments, including neurons, may be uniquely sensitized by social defeat-induced interleukin-1 (IL-1) signaling. Therefore, the aim of this study was to determine if glutamatergic neuronal IL-1 receptor signaling was essential in promoting stress-sensitization after social defeat. Here, wild-type (IL-1R1+/+) mice and mice with IL-1 receptor-1 deleted selectively in glutamatergic neurons (Vglut2-IL-1R1-/-) were stress-sensitized by social defeat (6-cycles) and then exposed to acute defeat (1-cycle) at day 30. Acute defeat-induced neuronal activation (ΔFosB and phospo-CREB) in the hippocampus of stress-sensitized mice was dependent on neuronal IL-1R1. Moreover, acute defeat-induced social withdrawal and working memory impairment in stress-sensitized mice were also dependent on neuronal IL-1R1. To address region and time dependency, an AAV2-IL-1 receptor antagonist construct was administered into the hippocampus after sensitization, but prior to acute defeat at day 30. Although stress-sensitized mice had increased hippocampal pCREB and decreased working memory after stress re-exposure, these events were not influenced by AAV2-IL-1 receptor antagonist. Hippocampal ΔFosB induction and corresponding social withdrawal in stress-sensitized mice after stress re-exposure were prevented by the AAV2-IL-1 receptor antagonist. Collectively, IL-1 signaling in glutamatergic neurons of the hippocampus was essential in neuronal-sensitization after social defeat and the recall of social withdrawal.

Staphylococcus aureus Carrier Types are not Evidence of Population Heterogeneity.

Asymptomatic colonization by Staphylococcus aureus is a precursor for infection, so identifying the mode and source of transmission which leads to colonization could help target interventions. Longitudinal studies have shown that some people are persistently colonized for years, while others seem to carry S. aureus for weeks or less, and conventional wisdom attributes this disparity to an underlying risk factor in the persistently colonized. We analyze published data with mathematical models of acquisition and carriage to compare this hypothesis with alternatives. The null model assumes a homogeneous population and still produces highly variable colonization durations (mean of 1.94 years, 5th percentile 0.1 years, 95th percentile 5.8 years). Simulations show that this inherent variability, combined with censoring in longitudinal cohort studies, is sufficient to produce the appearance of "persistent carriers," "intermittent carriers," and "noncarriers" in data. Our estimates for colonization duration exhibit sensitivity to the assumption that false positives can occur despite being rare, but our model-based approach simultaneously estimates specificity and sensitivity along with epidemiological parameters. Our results show it is plausible that S. aureus colonizes people indiscriminately, and improved understanding of the types of exposures which result in colonization is essential.

Do more with Less: Improving High Parameter Cytometry Through Overnight Staining.

Recent advances in flow cytometry have allowed high-dimensional characterization of biological phenomena, enabling breakthroughs in a multitude of fields. Despite the appreciation of the unique properties of antigens and fluorophores in high-parameter panel design, staining conditions are often standardized for short surface stains, regardless of antibody affinity or antigen accessibility. Here, we demonstrate how increasing antibody incubation times can lead to substantial improvements in sensitivity, maintaining specificity, and reducing background, while also significantly reducing the costs of high-parameter cytometry panels. Furthermore, overnight staining reduces the influence of interexperimental variability, assisting accurate pooling over experiments over extended time courses. We provide guidance on how to optimize staining conditions for diverse antigens, including how different fixation strategies can affect epitope accessibility. Overnight staining can thus substantially improve the resolution, repeatability, and cost-effectiveness of high-parameter cytometry. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.

InAs/MoRe Hybrid Semiconductor/Superconductor Nanowire Devices.

Implementing superconductors capable of proximity-inducing a large energy gap in semiconductors in the presence of strong magnetic fields is a major goal toward applications of semiconductor/superconductor hybrid materials in future quantum information technologies. Here, we study the performance of devices consisting of InAs nanowires in electrical contact with molybdenum-rhenium (MoRe) superconducting alloys. The MoRe thin films exhibit transition temperatures of ∼10 K and critical fields exceeding 6 T. Normal/superconductor devices enabled tunnel spectroscopy of the corresponding induced superconductivity, which was maintained up to ∼10 K, and MoRe-based Josephson devices exhibited supercurrents and multiple Andreev reflections. We determine an induced superconducting gap lower than expected from the transition temperature and observe gap softening at finite magnetic field. These may be common features for hybrids based on large-gap, type II superconductors. The results encourage further development of MoRe-based hybrids.

Electrophysiologically Determined Spectral Responses in Lobesia botrana (Lepidoptera: Tortricidae).

Electrophysiological methods were used to test the visual sensitivity of European grapevine moth, Lobesia botrana (Lepidoptera: Tortricidae) to wavelengths ranging from 300 to 700 nm. For male and females tested, a main, peak response occurred in the 460-540 nm range (blue-green wavelengths) with females having a generally lower response to wavelengths in that range. A second smaller peak was observed for both sexes at the 340-420 nm range. A general linear model indicated that males, virgin females, and mated females did not react differently to changes in wavelength. No moths showed any obvious sensitivity to wavelengths between 580 and 700 nm. Based on our retinal recording data we suggest that UV light traps (≤480 nm) could be utilized alongside pheromone traps when monitoring L. botrana in high risk areas.

Mass spectrometry in organic and bio-organic catalysis: Using thermochemical properties to lend insight into mechanism.

In this review, we discuss gas phase experimentation centered on the measurement of acidity and proton affinity of substrates that are useful for understanding catalytic mechanisms. The review is divided into two parts. The first covers examples of organocatalysis, while the second focuses on biological catalysis. The utility of gas phase acidity and basicity values for lending insight into mechanisms of catalysis is highlighted.

Subtype-specific responses of hKv7.4 and hKv7.5 channels to polyunsaturated fatty acids reveal an unconventional modulatory site and mechanism.

The KV7.4 and KV7.5 subtypes of voltage-gated potassium channels play a role in important physiological processes such as sound amplification in the cochlea and adjusting vascular smooth muscle tone. Therefore, the mechanisms that regulate KV7.4 and KV7.5 channel function are of interest. Here, we study the effect of polyunsaturated fatty acids (PUFAs) on human KV7.4 and KV7.5 channels expressed in Xenopus oocytes. We report that PUFAs facilitate activation of hKV7.5 by shifting the V50 of the conductance versus voltage (G(V)) curve toward more negative voltages. This response depends on the head group charge, as an uncharged PUFA analogue has no effect and a positively charged PUFA analogue induces positive V50 shifts. In contrast, PUFAs inhibit activation of hKV7.4 by shifting V50 toward more positive voltages. No effect on V50 of hKV7.4 is observed by an uncharged or a positively charged PUFA analogue. Thus, the hKV7.5 channel's response to PUFAs is analogous to the one previously observed in hKV7.1-7.3 channels, whereas the hKV7.4 channel response is opposite, revealing subtype-specific responses to PUFAs. We identify a unique inner PUFA interaction site in the voltage-sensing domain of hKV7.4 underlying the PUFA response, revealing an unconventional mechanism of modulation of hKV7.4 by PUFAs.

In order to carry out their roles in the body, cells need to send and receive electrical signals. They can do this by allowing ions to move in and out through dedicated pore-like structures studded through their membrane. These channels are specific to one type of ions, and their activity ­ whether they open or close ­ is carefully controlled. In humans, defective ion channels are associated with conditions such as irregular heartbeats, epileptic seizures or hearing loss. Research has identified molecules known as polyunsaturated fatty acids as being able to control the activity of certain members of the K_V7 family of potassium ion channels. The K_V7.1 and K_V7.2/7.3 channels are respectively present in the heart and the brain; K_V7.4 is important for hearing, while K_V7.5 plays a key role in regulating muscle tone in blood vessels. Polyunsaturated fatty acids can activate K_V7.1 and K_V7.2/7.3 but their impact on K_V7.4 and K_V7.5 remains unclear. Frampton et al. explored this question by studying human K_V7.4 and K_V7.5 channels expressed in frog egg cells. This showed that fatty acids activated K_V7.5 (as for K_V7.1 and K_V7.2/7.3), but that they reduced the activity of K_V7.4. Closely examining the structure of K_V7.4 revealed that the fatty acids were binding to a different region compared to the other K_V7 channels. When this site was made inaccessible, fatty acids increased the activity of K_V7.4, just as for the rest of the family. These results may help to understand the role of polyunsaturated fatty acids in the body. In addition, knowing how these molecules interact with channels in the same family will be useful for optimising a drug's structure to avoid side effects. However, further research will be needed to understand the broader impact in a more complex biological organism.

Commodity Polymers to Functional Aminated Materials: Single-Step and Atom-Economic Synthesis by Hydroaminoalkylation.

Hydroaminoalkylation (HAA) is demonstrated to be a promising postpolymerization route to catalytically prepare amine-functionalized atactic polypropylene. Using a recently reported tantalum catalyst supported by a N,O-chelating cyclic ureate ligand, vinyl-terminated polypropylene (VTPP) is transformed into both aryl and alkyl secondary amine-terminated polyolefins. Early transition-metal-catalyzed hydroaminoalkylation avoids protection/deprotection protocols typically required for secondary amine synthesis. This single-step reaction can be performed at multigram scale with minimal solvent and is atom economic, thereby allowing for optimized product isolation. Materials are characterized by multinuclear NMR spectroscopy, IR spectroscopy, DSC, and TGA. The utility of the reactive and unprotected amine terminus is highlighted by the installation of a fluorescent end group and the assembly of a graft copolymer by condensation of the secondary amine terminus with carboxylic acid moieties.

Incidental findings on single-photon emission computed tomography/computed tomography (SPECT/CT) lymphoscintigraphy in breast cancer: the proposed Westmead SPECT/CT incidental findings classification.

BACKGROUND: The aim of this study is to determine the prevalence of incidental radiological findings detected on SPECT/CT performed as part of pre-operative lymphoscintigraphy for sentinel lymph node biopsy (SLNB) in patients undergoing breast cancer surgery and development of a modified classification to workup these lesions. METHODS: A retrospective audit was performed of all SPECT/CT performed in combination with lymphoscintigrams in breast cancer patients presenting with clinically node negative axillae and operated on by breast surgeons at the Westmead Breast Cancer Institute over a 12-month period. RESULTS: Four hundred and nineteen patients were included in the study. In 149 patients (35.6%), there was a total of 205 incidental findings. The most common findings were, pulmonary abnormalities (38.5%), abdominal findings (27.8%), thyroid nodules (14.6%), cardiac abnormalities (10.7%) and others (8.3%). Using our proposed Westmead SPECT/CT incidental findings (WSIF) classification, 7.8% were known, 17.6% were major findings, 48.3% were minor findings, 15.1% were minimal findings and 11.2% were equivocal findings. 17.6% (n = 36) underwent further workup and investigation and 3.4% of patients (n = 5) required therapeutic intervention, including chemotherapy for primary lung cancer(n = 1) and surgeries (thoracotomy, n = 1; thyroidectomy, n = 2; colonoscopy, n = 1). 93.8% (n = 393) had at least one SLN mapped, most commonly located in Level 1 of the axilla. CONCLUSION: The incidental findings on SPECT/CT in combination with lymphoscintigraphy is within the range of previous studies (27.3-59.5%). A small proportion of patients required significant major interventions (3.4%). We propose that all incidental findings should be assessed according to our WSIF classification to aid in triaging need for further investigation and management.

Comparison of an automated smartphone-based smoking cessation intervention versus standard quitline-delivered treatment among underserved smokers: protocol for a randomized controlled trial.

BACKGROUND: Smoking is the leading cause of preventable morbidity and mortality in the United States. Individuals with low socioeconomic status have disproportionately high smoking rates and greater difficulty quitting smoking. Efficiently connecting underserved smokers to effective tobacco cessation programs is crucial for disease prevention and the elimination of health disparities. Smartphone-based interventions have the potential to enhance the reach and efficacy of smoking cessation treatments targeting underserved smokers, but there is little efficacy data for these interventions. In this study, we will partner with a large, local hunger-relief organization to evaluate the efficacy and economic impact of a theoretically-based, fully-automated, and interactive smartphone-based smoking cessation intervention. METHODS: This study will consist of a 2-group randomized controlled trial. Participants (N = 500) will be recruited from a network of food distribution centers in West Central Florida and randomized to receive either Standard Treatment (ST, n = 250) or Automated Treatment (AT, n = 250). ST participants will be connected to the Florida Quitline for telephone-based treatment and will receive a 10-week supply of nicotine replacement therapy (NRT; transdermal patches and lozenges). AT participants will receive 10 weeks of NRT and a fully-automated smartphone-based intervention consisting of interactive messaging, images, and audiovisual clips. The AT intervention period will span 26 weeks, with 12 weeks of proactive content and 26 weeks of on-demand access. ST and AT participants will complete weekly 4-item assessments for 26 weeks and 3-, 6-, and 12-month follow-up assessments. Our primary aim is to evaluate the efficacy of AT in facilitating smoking abstinence. As secondary aims, we will explore potential mediators and conduct economic evaluations to assess the cost and/or cost-effectiveness of ST vs. AT. DISCUSSION: The overall goal of this project is to determine if AT is better at facilitating long-term smoking abstinence than ST, the more resource-intensive approach. If efficacy is established, the AT approach will be relatively easy to disseminate and for community-based organizations to scale and implement, thus helping to reduce tobacco-related health disparities. TRIAL REGISTRATION: Clinical Trials Registry NCT05004662 . Registered August 13, 2021.

Dynamic Interleukin-1 Receptor Type 1 Signaling Mediates Microglia-Vasculature Interactions Following Repeated Systemic LPS.

Introduction: Lipopolysaccharide (LPS) preconditioning involves repeated, systemic, and sub-threshold doses of LPS, which induces a neuroprotective state within the CNS, thus preventing neuronal death and functional losses. Recently, proinflammatory cytokine, Interleukin-1 (IL-1), and its primary signaling partner, interleukin-1 receptor type 1 (IL-1R1), have been associated with neuroprotection in the CNS. However, it is still unknown how IL-1/IL-1R1 signaling impacts the processes associated with neuroprotection. Methods: Using our IL-1R1 restore genetic mouse model, mouse lines were generated to restrict IL-1R1 expression either to endothelia (Tie2-Cre-Il1r1r/r) or microglia (Cx3Cr1-Cre-Il1r1 r/r), in addition to either global ablation (Il1r1 r/r) or global restoration of IL-1R1 (Il1r1 GR/GR). The LPS preconditioning paradigm consisted of four daily i.p. injections of LPS at 1 mg/kg (4d LPS). 24 hrs following the final i.p. LPS injection, tissue was collected for qPCR analysis, immunohistochemistry, or FAC sorting. Results: Following 4d LPS, we found multiple phenotypes that are dependent on IL-1R1 signaling such as microglia morphology alterations, increased microglial M2-like gene expression, and clustering of microglia onto the brain vasculature. We determined that 4d LPS induces microglial morphological changes, clustering at the vasculature, and gene expression changes are dependent on endothelial IL-1R1, but not microglial IL-1R1. A novel observation was the induction of microglial IL-1R1 (mIL-1R1) following 4d LPS. The induced mIL-1R1 permits a unique response to central IL-1ß: the mIL-1R1 dependent induction of IL-1R1 antagonist (IL-1RA) and IL-1ß gene expression. Analysis of RNA sequencing datasets revealed that mIL-1R1 is also induced in neurodegenerative diseases. Discussion: Here, we have identified cell type-specific IL-1R1 mediated mechanisms, which may contribute to the neuroprotection observed in LPS preconditioning. These findings identify key cellular and molecular contributors in LPS-induced neuroprotection.

Stressor-Induced Reduction in Cognitive Behavior is Associated with Impaired Colonic Mucus Layer Integrity and is Dependent Upon the LPS-Binding Protein Receptor CD14.

Purpose: Commensal microbes are impacted by stressor exposure and are known contributors to cognitive and social behaviors, but the pathways through which gut microbes influence stressor-induced behavioral changes are mostly unknown. A murine social stressor was used to determine whether host-microbe interactions are necessary for stressor-induced inflammation, including neuroinflammation, that leads to reduced cognitive and social behavior. Methods: C57BL/6 male mice were exposed to a paired fighting social stressor over a 1 hr period for 6 consecutive days. Y-maze and social interaction behaviors were tested following the last day of the stressor. Serum cytokines and lipopolysaccharide binding protein (LBP) were measured and the number and morphology of hippocampal microglia determined via immunohistochemistry. Intestinal mucous thickness and antimicrobial peptide expression were determined via fluorescent staining and real-time PCR (respectively) and microbial community composition was assessed using 16S rRNA gene amplicon sequencing. To determine whether the microbiota or the LBP receptor (CD14) are necessary for stressor-induced behavioral changes, experiments were performed in mice treated with a broad-spectrum antibiotic cocktail or in CD14-/- mice. Results: The stressor reduced Y-maze spontaneous alternations, which was accompanied by increased microglia in the hippocampus, increased circulating cytokines (eg, IL-6, TNF-α) and LBP, and reduced intestinal mucus thickness while increasing antimicrobial peptides and cytokines. These stressor-induced changes were largely prevented in mice given broad-spectrum antibiotics and in CD14-/- mice. In contrast, social stressor-induced alterations of social behavior were not microbe-dependent. Conclusion: Stressor-induced cognitive deficits involve enhanced bacterial interaction with the intestine, leading to low-grade, CD14-dependent, inflammation.

Blocking the human common beta subunit of the GM-CSF, IL-5 and IL-3 receptors markedly reduces hyperinflammation in ARDS models.

Acute respiratory distress syndrome (ARDS) is triggered by various aetiological factors such as trauma, sepsis and respiratory viruses including SARS-CoV-2 and influenza A virus. Immune profiling of severe COVID-19 patients has identified a complex pattern of cytokines including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-5, which are significant mediators of viral-induced hyperinflammation. This strong response has prompted the development of therapies that block GM-CSF and other cytokines individually to limit inflammation related pathology. The common cytokine binding site of the human common beta (ßc) receptor signals for three inflammatory cytokines: GM-CSF, IL-5 and IL-3. In this study, ßc was targeted with the monoclonal antibody (mAb) CSL311 in engineered mice devoid of mouse ßc and ßIL-3 and expressing human ßc (hßcTg mice). Direct pulmonary administration of lipopolysaccharide (LPS) caused ARDS-like lung injury, and CSL311 markedly reduced lung inflammation and oedema, resulting in improved oxygen saturation levels in hßcTg mice. In a separate model, influenza (HKx31) lung infection caused viral pneumonia associated with a large influx of myeloid cells into the lungs of hßcTg mice. The therapeutic application of CSL311 potently decreased accumulation of monocytes/macrophages, neutrophils, and eosinophils without altering lung viral loads. Furthermore, CSL311 treatment did not limit the viral-induced expansion of NK and NKT cells, or the tissue expression of type I/II/III interferons needed for efficient viral clearance. Simultaneously blocking GM-CSF, IL-5 and IL-3 signalling with CSL311 may represent an improved and clinically applicable strategy to reducing hyperinflammation in the ARDS setting.

Mobile contingency management for smoking cessation among socioeconomically disadvantaged adults: Protocol for a randomized trial.

BACKGROUND: Smoking rates remain high among socioeconomically disadvantaged adults. Offering small escalating financial incentives for abstinence (i.e., contingency management [CM]), alongside clinic-based treatment dramatically increases cessation rates in this vulnerable population. However, innovative approaches are needed for those who are less able to attend office visits. The current study will evaluate an automated mobile phone-based CM approach that will allow socioeconomically disadvantaged individuals to remotely earn financial incentives for smoking cessation. METHODS: The investigators have previously combined technologies, including 1) carbon monoxide monitors that connect with mobile phones to remotely verify abstinence, 2) facial recognition software to confirm identity during breath sample submissions, and 3) automated delivery of incentives triggered by biochemical abstinence confirmation. This automated CM approach will be evaluated in a randomized controlled trial of 532 low-income adults seeking cessation treatment. Participants will be randomly assigned to telephone counseling and nicotine replacement therapy (standard care [SC]) or SC plus mobile financial incentives (CM) for abstinence. RESULTS: Biochemically-verified 7-day point prevalence abstinence at 26 weeks post-quit is the primary outcome. The cost-effectiveness of the interventions will be evaluated. Potential treatment mechanisms, including self-efficacy, motivation, and treatment engagement, will be explored to optimize future interventions. DISCUSSION: Automated mobile CM may offer a low-cost approach to smoking cessation that can be combined with telephone counseling and pharmacological interventions. This approach represents a critical step toward the widespread dissemination of CM treatment to real-world settings, to reduce tobacco-related disease and disparities.

In Search of Coronary Thrombosis as the Cause of Myocardial Infarction: Unraveling a 20th-Century Mystery.

For the greater part of the 20th century, the pathophysiology of acute myocardial infarction regarding whether thrombosis was either present or primary was debated until 1973 when pathologists and clinicians met and by consensus, finally decided that the data supported that transmural infarction (what we now refer to as ST elevation myocardial infarction or STEMI) was caused by thrombus in the vessel supplying the infarcted territory. As the data for this consensus came from pathological analysis, it took another 7 years until angiographic and interventional data in humans with acute presentations of transmural infarction convincingly indicated that thrombus was indeed responsible. Subsequently, in patients presenting with either syndromes of unstable angina or nontransmural (later called non-ST elevation) myocardial infarction, it was established through angiographic and other interventional approaches that thrombus formation was also causative in a substantial proportion of these patients. This article reviews the history and this search for causation of myocardial infarction that now has resulted in present therapies that have saved innumerable lives over the last 30 to 40 years.

Andreev Interference in the Surface Accumulation Layer of Half-Shell InAsSb/Al Hybrid Nanowires.

Understanding the spatial distribution of charge carriers in III-V nanowires proximity coupled to superconductors is important for the design and interpretation of experiments based on hybrid quantum devices. In this letter, the gate-dependent surface accumulation layer of half-shell InAsSb/Al nanowires is studied by means of Andreev interference in a parallel magnetic field. Both uniform hybrid nanowires and devices featuring a short Josephson junction fabricated by shadow lithography, exhibit periodic modulation of the switching current. The period corresponds to a flux quantum through the nanowire diameter and is consistent with Andreev bound states occupying a cylindrical surface accumulation layer. The spatial distribution is tunable by a gate potential as expected from electrostatic models.