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Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) is a pathogenic coronavirus causing COVID‐19 infection. The interaction between the SARS‐CoV‐2 spike protein and the human receptor angiotensin‐converting enzyme 2, both of which contain several cysteine residues, is impacted by the disulfide‐thiol balance in the host cell. The host cell redox status is affected by oxidative stress due to the imbalance between the reactive oxygen/nitrogen species and antioxidants. Recent studies have shown that Vitamin D supplementation could reduce oxidative stress. It has also been proposed that vitamin D at physiological concentration has preventive effects on many viral infections, including COVID‐19. However, the molecular‐level picture of the interplay of vitamin D deficiency, oxidative stress, and the severity of COVID‐19 has remained unclear. Herein, we present a thorough review focusing on the possible molecular mechanism by which vitamin D could alter host cell redox status and block viral entry, thereby preventing COVID‐19 infection or reducing the severity of the disease.

Condyloma lata, a cutaneous manifestation of secondary syphilis, typically presents as verrucous papules or plaques in the anogenital area. Here, we present a case of secondary syphilis presenting in a 38-year-old man as condyloma latum of the plantar foot in the absence of other cutaneous findings of secondary syphilis. The plantar foot is an unusual location for condyloma lata which has not previously been reported in the medical literature. Histopathology was essential to diagnosis in this case and demonstrated verrucous epidermal hyperplasia with a plasma cell-rich infiltrate in the dermis and innumerable spirochetes in the epidermis. The patient was successfully treated with intramuscular penicillin benzathine G. Given the recent rise in the incidence of primary and secondary syphilis, it is essential for clinicians to be aware of atypical presentations of secondary syphilis to avoid delays in treatment and decrease the risk of transmission to sexual partners.

Introduction Most adult cigarette smokers who use e-cigarettes are dual cigarette and e-cigarette (CC-EC) users, yet little is known about relative consumption of cigarettes to e-cigarettes and any associated harm reduction. Methods Rate of substitution from cigarettes to e-cigarettes at week 6 and change in biomarkers of exposure and potential harm were examined among dual dual cigarette and e-cigarette users [64/114 (56%); 35 Black, 29 Latino] in an e-cigarette switching randomized trial. Results Dual users averaged 79% substitution of cigarettes for e-cigarettes at week 6, resulting in a reduction from baseline of 70.0 ± 54.1 cigarettes per week (p < .001). Total nicotine consumption remained stable (baseline: 1160.5 ± 1042.1 pg/mL of cotinine, week 6: 1312.5 ± 1725.9 pg/mL of cotinine, p = .47), while significant reductions were seen in the potent lung carcinogen 4-(methylnitrosamino)-1-(3-pyridul)-1-butanol (NNAL) (-55.9 ± 88.6 ng/ml, p < .001), carbon monoxide (-6.3 ± 8.6 ppm, p < .001), and self-reported respiratory symptoms (−3.3 ± 8.0, p = .002). No significant changes were found in blood pressure or spirometry. Greater substitution from cigarettes to e-cigarettes was associated with larger reductions in NNAL (r = −.29, p = .02). Conclusions The predominant dual-use pattern was characterized by regular e-cigarette and intermittent cigarette use. Findings demonstrate the short-term harm reduction potential of this dual-use pattern in Black and Latino smokers and suggest that the greatest benefit, aside from cessation of both products, is achieved by higher substitution of e-cigarettes for cigarettes. Findings need confirmation in a larger sample with longer follow-up in dual users with greater variability in the rate of substitution. ClinicalTrials.gov Identifier NCT03511001 Implications Findings suggest short-term harm reduction potential of dual cigarette-e-cigarette use for Black and Latino smokers. Results also demonstrate the heterogeneity of dual-use, with the greatest harm reduction seen in dual users with higher rates of substitution from cigarettes to e-cigarettes. Study results should be confirmed in a full clinical trial with long-term follow-up to evaluate maintenance of dual-use patterns and associated harm reduction potential over time.

Rubinstein-Taybi syndrome (RSTS) is an autosomal dominant genetic syndrome characterized by distinct facial features, broad thumbs, growth restriction, microcephaly, intellectual disability, and developmental delay. Pathogenic variants in both CREBBP and EP300 have been associated with RSTS. Here we present a case of a female with hyperinsulinism and features consistent with RSTS, found to have a pathogenic variant in EP300. While there have been a few rare case reports of hyperinsulinism in RSTS, we suggest that hyperinsulinism might be a more prominent feature in EP300 variant RSTS than previously recognized.

Activated T cells drive a range of immune-mediated inflammatory diseases. LAG-3 is transiently expressed on recently activated CD4+ and CD8+ T cells. We describe the engineering and first-in-human clinical study (NCT02195349) of GSK2831781 (an afucosylated humanized IgG1 monoclonal antibody enhanced with high affinity for Fc receptors and LAG-3 and antibody-dependent cellular cytotoxicity capabilities), which depletes LAG-3 expressing cells. GSK2831781 was tested in a phase I/Ib, double-blind, placebo-controlled clinical study, which randomized 40 healthy participants (part A) and 27 patients with psoriasis (part B) to single doses of GSK2831781 (up to 0.15 and 5 mg/kg, respectively) or placebo. Adverse events were generally balanced across groups, with no safety or tolerability concern identified. LAG-3+ cell depletion in peripheral blood was observed at doses ≥ 0.15 mg/kg and was dose-dependent. In biopsies of psoriasis plaques, a reduction in mean group LAG-3+ and CD3+ T-cell counts was observed following treatment. Downregulation of proinflammatory genes (IL-17A, IL-17F, IFNγ, and S100A12) and upregulation of the epithelial barrier integrity gene, CDHR1, was observed with the 5 mg/kg dose of GSK2831781. Psoriasis disease activity improved up to day 43 at all GSK2831781 doses (0.5, 1.5, and 5 mg/kg) compared with placebo. Depletion of LAG-3-expressing activated T cells is a novel approach, and this first clinical study shows that GSK2831781 is pharmacologically active and provides encouraging early evidence of clinical effects in psoriasis, which warrants further investigation in T-cell-mediated inflammatory diseases.

OBJECTIVE: To assess the impact of separation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR)-positive mother-newborn dyads on breastfeeding outcomes. STUDY DESIGN: This observational longitudinal cohort study of mothers with SARS-CoV-2 PCR-and their infants at 3 NYU Langone Health hospitals was conducted between March 25, 2020, and May 30, 2020. Mothers were surveyed by telephone regarding predelivery feeding plans, in-hospital feeding, and home feeding of their neonates. Any change prompted an additional question to determine whether this change was due to coronavirus disease-2019 (COVID-19). RESULTS: Of the 160 mother-newborn dyads, 103 mothers were reached by telephone, and 85 consented to participate. There was no significant difference in the predelivery feeding plan between the separated and unseparated dyads (P = .268). Higher rates of breastfeeding were observed in the unseparated dyads compared with the separated dyads both in the hospital (P

Nodular secondary syphilis is an uncommon variant of secondary syphilis. We identified three cases of nodular secondary syphilis at our institution. The first patient presented with a diffuse nodular rash that included his scrotum and penis. The second patient had disseminated skin-colored nodules with serosanguinous crust on his face, trunk, and extremities. The third patient had a pruritic papular and nodular rash with overlying crust. All three patients had a reactive rapid plasma reagin and tested positive for fluorescent treponemal antibody absorption. All were eventually confirmed to be human immunodeficiency virus-positive. Histopathological examination demonstrated inflammatory infiltrate in the dermis composed of lymphocytes, histiocytes, and plasma cells, and treponemal staining highlighted spirochetes in the dermis. The patients were successfully treated with intramuscular penicillin benzathine G. Physicians should be aware of nodular syphilis as a less common cutaneous manifestation of secondary syphilis. Prompt diagnosis of secondary syphilis can expedite resolution of the infection and avoid progression to tertiary syphilis.

Using a checklist to establish patients' level of dependence and combining behavioral therapy with nicotine replacement products can help users to quit.

Almost all spatial domain image steganography methods rely on modifying the Least Significant Bits (LSB) of each pixel to minimize the visual distortions. However, these methods are susceptible to LSB blind attacks and quantitative steganalyses. This paper presents an adaptive spatial domain image steganography algorithm for hiding digital media based on matrix patterns, named “Adaptive Matrix Pattern” (AMP). The AMP method increases the security of the steganography scheme of largely hidden messages since it adaptively generates a unique codebook matrix pattern for each ASCII character in each image block. Therefore, each ASCII character gets a different codebook matrix pattern even in different regions of the same image. Moreover, it uses a preprocessing algorithm to identify the most suitable image blocks for hiding purposes. The resulting stego-images are robust against LSB blind attacks since the middle bits of green and blue channels generate matrix patterns and hiding secrets, respectively. Experimental results show that AMP is robust against quantitative steganalyses. Additionally, the quality of stego-images, based on the peak signal-to-noise ratio metric, remains high in both stego-RGB-image and in the stego-blue-channel. Finally, the AMP method provides a high hiding capacity, up to 1.33 bits per pixel.

Reasons for Black-White disparities in smoking abstinence are not well understood. This study examined area-level socioeconomic disadvantage as a contributor to lower quit rates for Blacks who smoke among 223 Black and 221 White low-income individuals who smoke enrolled in a smoking cessation trial. Outcome was cotinine-verified abstinence at week 26. Census tract-level disadvantage was measured using 5-year estimates linked to participants’ home address and included percentage of: female headed households; public assistance; unemployed; < 100% of the federal poverty level; and whether there was > 25% having less than a high school education. A neighborhood disadvantage index score (DIS) was calculated as the sum of z-scores for each variable. Black participants lived in more disadvantaged areas than White participants [DIS mean (SD): 3.2 (4.3), −1.0 (3.2), p < 0.001]. Similar rates of abstinence were observed at the same level of disadvantage [DIS ≥ 50th percentile (less disadvantage): 21.9% Blacks, 26.2% Whites, p = 0.50; DIS < 50th percentile (more disadvantage): 10.7% Blacks, 15.8% Whites, p = 0.31]. Only DIS but neither race nor the interaction was retained in the final model predicting abstinence; each unit increase in DIS was associated with 9% reduced odds of abstinence (OR: 0.91, 95% CI: 0.87, 0.96). Findings point to the importance of examining factors associated with race that contribute to health inequities and underscore the need to consider how consequences of systemic racism, such as neighborhood context and other consequences not captured by the DIS, can constrain or facilitate smoking cessation when developing interventions.

INTRODUCTION: Polytobacco use and experimentation is common among young adults. Additional research is needed to determine how these patterns of use impact perceptions of tobacco-related harm and risk. The current study examined whether a relationship exists between an increased number of tobacco products used and decreases in perceptions of harmfulness and health risk. METHOD: Participants (N = 792) completed a survey assessing current/lifetime tobacco use, perceived absolute harmfulness of tobacco/nicotine products and perceived health risk of smoking. For some analyses, participants were grouped by polytobacco use status. RESULTS: Among participants who ever tried a tobacco product, a greater number of products tried was associated with lower perceptions of harm (all p < .05). For e-cigarettes and hookah, nonusers rated tobacco products as more harmful compared to single product, dual, and poly users (all p < .05). Number of products tried predicted perceived harmfulness above and beyond demographic characteristics and polytobacco use status across all products. Similarly, number of products tried predicted perceived health risk above and beyond demographic characteristics and polytobacco use status for both lung cancer and heart disease risk. DISCUSSION: Trying a greater number of tobacco products is associated with lower perceived harmfulness of tobacco products. Prospective studies are needed to determine if experimentation with more tobacco products leads to reductions in perceived risk of tobacco use and subsequent sustained use of tobacco.

Introduction Relative to non-waterpipe (WP) smokers, WP smokers are more than twice as likely to use alcohol and frequently consume alcohol before or during smoking sessions. Co-use of alcohol and WP may result in greater toxicant exposure compared to WP smoking alone. To date, no study systematically has investigated the impact of acute alcohol intoxication on WP smoking topography, exposure to tobacco-related toxicants, or abuse liability. Methods Dyads of current WP smokers and drinkers (N = 42; age = 21–32 years) completed two in-laboratory ad libitum smoking sessions (≤2 hours) following 12-hour nicotine abstinence in a double-blind, randomized crossover design in which they consumed a placebo versus active drink (sustained breath alcohol concentration = .08). Exhaled carbon monoxide (eCO) and plasma nicotine concentration were assessed. Questionnaires assessed smoking experience and smoking urge. Smoking topography was measured continuously throughout each smoking session. Results The alcohol session was associated with increased inhaled volume, flow rate, and WP session duration compared to placebo. Compared to placebo, participants reported a more positive overall smoking experience following the alcohol session and greater smoking urges pre- and post-smoking session. Although both sessions resulted in significant increases in eCO and plasma nicotine, no significant differences emerged in eCO or nicotine exposure between the active and placebo sessions. Conclusions Co-use of alcohol and WP may contribute to the maintenance of WP smoking through enhanced smoking experiences, increased urge to smoke, and significant exposure to addictive nicotine. Regulations may be necessary to limit the sale of alcohol in WP smoking lounges and reduce exposure to secondhand smoke. Implications The findings suggest co-use of alcohol and WP tobacco likely maintain WP use and dependence by enhancing the smoking experience and increasing urges to smoke. These findings have implications for regulations aimed at limiting co-use of alcohol and WP tobacco in WP lounges and limiting exposure to secondhand smoke. Clinical trials registration NCT03096860

Automated program repair (APR) techniques have shown a promising ability to generate patches that fix program bugs automatically. Typically such APR tools are dynamicin the sense that they find bugs by testing and they validate patches by running a program's test suite. Patches can also be validated manually. However, neither of these methods for validating patches can truly tell whether a patch is correct. Test suites are usually incomplete, and thus APR-generated patches may pass the tests but not be truly correct; in other words, the APR tools may be overfittingto the tests. The possibility of test overfitting leads to manual validation, which is costly, potentially biased, and can also be incomplete. Therefore, we must move past these methods to truly assess APR's overfitting problem. We aim to evaluate the test overfitting problem in dynamic APR tools using ground truth given by a set of programs equipped with formal behavioral specifications. Using these formal specifications and an automated verification tool, we found that there is definitely overfitting in the generated patches of seven well-studied APR tools, although many (about 59%) of the generated patches were indeed correct. Our study further points out two new problems that can affect APR tools: changes to the complexity of programs and numeric problems.An additional contribution is that we introduce the first publicly available data set of formally specified and verified Java programs, their test suites, and buggy variants, each of which has exactly one bug. &nbsp

Software is widely used in critical systems. Thus, it is important that developers can quickly find semantic bugs with testing; however, semantic bugs can only be revealed by tests that use valid inputs. Guided fuzzers can create input tests that cover all branches; however, they may not necessarily cover all branches with valid inputs. Therefore, the problem is how to guide a fuzzer to cover all branches in a program with only valid inputs. We perform a study of an idea that guarantees that all inputs generated by a guided fuzzer that reach the program under test are valid using formal specifications and runtime assertion checking. Our results show that this idea improves the feedback given to a guided fuzzer.

Individuals with diabetes insipidus who have an absent thirst mechanism can be challenging to manage, and are at increased risk of sodium derangements compared with those who have intact thirst. While adipsia can be associated with multiple underlying causes of DI, it occurs most commonly in patients following pituitary surgery, particularly after craniopharyngioma removal. The diagnosis can typically be made based on historical questions or following an episode of hypernatremia without a reported increase in thirst from the patient. Management includes increased home monitoring of body weight, fluid intake and output, and more frequent laboratory sodium monitoring. While the use of handheld blood analyzers to monitor sodium levels at home is not FDA-approved or commonplace, this can be useful in patients who are otherwise difficult to manage.

Background Adults experiencing homelessness have higher rates of disease and premature morbidity compared to the general population. Tobacco use is a primary contributing factor to these disparities; however, less is known regarding e-cigarette use patterns among adults experiencing homelessness and whether e-cigarettes are used in a manner that is narrowing or widening health disparities. This study aimed to describe the 1) prevalence and trends in e-cigarette use, 2) correlates of e-cigarettes use, and 3) rates of chronic health conditions by product use pattern in a community-based sample of adults experiencing homelessness. Methods Adults experiencing homelessness in Minnesota were surveyed by self-report in 2015 (n = 3672) and 2018 (n = 4181) regarding e-cigarette and combustible cigarette use, potential correlates of e-cigarette use, and self-reported chronic health conditions (i.e., asthma, hypertension, diabetes, and cancer). Results Frequency of use increased from 2015 to 2018 for combustible cigarettes (66.9% vs. 72.3%), e-cigarettes (11.4% vs. 14.5%), and dual combustible/e-cigarette use (10.2% vs. 12.9%). The strongest bivariate correlates of past 30-day e-cigarette use were younger age, non-binary gender identification, non-heterosexual orientation, identification as White/Caucasian, greater frequency of lifetime homelessness, substance use, lack of regular place for medical care, mental health diagnosis, criminal justice involvement, and combustible cigarette smoking. Dual users had significantly higher rates of asthma and cancer than both those using combustible cigarettes and those using neither combustible nor e-cigarettes. Conclusions During a time when cigarette smoking, e-cigarette use, and dual use were decreasing in the general population in Minnesota, rates increased in the homeless population. We observed that the rates of dual use were more than five times greater among homeless adults compared to the general population in 2018. Correlates of e-cigarette use were identified and should be used to identify subpopulations for intervention targeting. Mechanisms of the relationship between dual use and increased risks of health conditions deserve further study.

Introduction To examine whether changes in select measures of e-cigarette puffing topography are associated with changes in smoking behavior. Methods Sixteen current cigarette smokers were instructed to completely switch from smoking combustible cigarettes to using e-cigarettes over a 2-week period. The study was completed in the Southern Midwestern region of the United States. Measures included demographics, smoking history, and cigarette dependence, as well as baseline and 2-week follow-up self-reported cigarettes per day, cigarette craving and urges, exhaled carbon monoxide readings, and e-cigarette usage data (puff number, puffing time, and average puff duration) collected via the e-cigarette built-in puff counter. Results Over the 2-week switching period, participants significantly reduced their cigarettes per day (~80% reduction, p < .0001). Although the number of e-cigarette puffs/day remained relatively stable (p > .05), the average total e-cigarette daily puffing time increased significantly (p = .001). Users’ average puff duration increased by 91 ms/puff/d (p < .001). The percentage decrease in cigarettes smoked per day was significantly and directly related to the slope of subjects’ average puff duration over time (r(13) = .62, p = .01), such that as cigarettes per day decreased, puff duration increased. Self-reported smoking urges remained relatively stable from baseline to the end of the 2-week period (p > .05). Conclusions Among smokers switching to an e-cigarette, greater increases in e-cigarette puff duration was associated with greater reductions in cigarette smoking. Implications The current study is one of the first to examine changes in smokers’ e-cigarette puffing behavior and associated changes in cigarette consumption as they attempt to completely switch to e-cigarettes. During a 2-week switching period, participants reduced their cigarettes per day. Moreover, although e-cigarette puffs per day remained relatively stable, users’ average puff duration increased significantly. Greater increases in e-cigarette puff duration were associated with greater reductions in cigarette smoking. Understanding how to effectively use an e-cigarette to best reduce and eventually quit smoking will be necessary as smokers increasingly turn to these products to facilitate possible cessation.

Background and Aims Lymphocyte activation gene [LAG]-3 is an immune checkpoint and its expression identifies recently activated lymphocytes that may contribute to inflammation. We investigated the role of LAG-3 by analysing its expression and function in immune cells from blood and tissue of patients with ulcerative colitis [UC]. Methods The phenotypic properties of LAG-3+ T cells were determined by flow cytometry, qRT-PCR and single-cell RNA-sequencing. LAG-3+ cells were quantified and correlated with disease activity. The functional effects of LAG-3+ cells were tested using a depleting anti-LAG-3 monoclonal antibody [mAb] in a mixed lymphocyte reaction [MLR]. Results LAG-3+ cells in the blood were negligible. LAG-3+ lymphocytes were markedly increased in inflamed mucosal tissue and both frequencies of LAG-3+ T cells and transcript levels of LAG3 correlated with endoscopic severity. LAG-3 expression was predominantly on effector memory T cells, and single-cell RNA-sequencing revealed LAG3 expression in activated and cytokine-producing T cell subsets. Foxp3+CD25hi Tregs also expressed LAG-3, although most mucosal Tregs were LAG-3−. Mucosal LAG-3+ cells produced mainly interferon γ [IFNγ] and interleukin-17A. LAG-3+ cell numbers decreased in patients who responded to biologics, and remained elevated in non-responders. Treatment with a depleting anti-LAG-3 mAb led to a reduction in proliferation and IFNγ production in an MLR. Conclusions LAG-3+ cells are increased in the inflamed mucosa, predominantly on effector memory T cells with an activated phenotype and their cell numbers positively correlate with disease activity. Depleting LAG-3 eliminates activated proliferating T cells, and hence LAG-3 could be a therapeutic target in UC.

Verrucous venous malformation, also known as verrucous hemangioma, is a superficial vascular malformation with a variable degree of hyperkeratosis that is composed of capillaries and veins in the dermis and sometimes subcutaneous tissue. We describe a 53-year-old man who presented with a large hyperkeratotic plaque of the left dorsal and plantar foot. Biopsy revealed verrucous acanthosis of the epidermis and a proliferation of thin-walled vessels in the dermis. We provide a brief review of the clinical and histopathologic presentation, differential diagnosis, and management of this rare entity.

Exposure to secondhand smoke (SHSe) can compound an already challenging set of health problems for youth with Sickle Cell Disease (SCD). Exposure to electronic cigarettes may also impact SCD symptomology and respiratory functioning. This study built on these previous findings by a) utilizing two objective measures of SHSe, salivary cotinine and exhaled carbon monoxide and b) examining the association of SHSe with emergency department utilization, physician-reported sickle cell crises, and pulmonary functioning. Caregivers (N=31 dyads; M(age)=37.6 years; SD=8.5 years) of youth with SCD (M(age)=9.0 years; SD=4.5 years) completed self-report measures of tobacco/nicotine use. Youth provided a saliva sample to assess cotinine levels, and performed pulmonary function tests. Dyads provided breath samples for measurement of eCO. A chart review was conducted to obtain medical history and utilization. Majority of youth (88%) were exposed to SHS via salivary cotinine. Interestingly, no significant associations were observed between youth cotinine levels and emergency department utilization, physician-reported sickle cell crises, or pulmonary functioning. Present findings indicate a need to assess for SHSe using objective assessment measures. Future research should investigate which specific factors contribute to increase SHSe/SHVe in youth with SCD.

Waterpipe (WP) tobacco smoking delivers many of the same harmful toxicants as cigarette smoking and is on the rise in the US. This study evaluated the feasibility and efficacy of a brief personalized feedback intervention in affecting changes in WP smoking among current WP smokers.Participants (N=109) were recruited as they entered WP lounges and completed a questionnaire and exhaled carbon monoxide (eCO) testing before entering the WP lounge. Participants were cluster-randomized to assessment-only control (AOC) or intervention conditions. The intervention condition received health risk information and personalized feedback on pre- and post-WP session eCO levels. Participants completed a survey at the end of the WP session and at 3-month follow-up.Compared to control, the intervention was effective in increasing knowledge of WP-related harms, correcting risk perceptions, increasing importance of quitting WP smoking, and increasing confidence in ability to quit WP smoking at post-WP session (p0.05). Differences were maintained for knowledge of WP-related harms, risk perceptions, and commitment to quitting WP at 3-month follow-up; however, no significant difference (p0.05) was observed in WP smoking (i.e., days smoked and number of WPs smoked) at 3-month follow-up between the intervention (M=3.97days, SD=9.83; M=6.45 bowls, SD=19.60) and control conditions (M=3.32days, SD=5.24; M=3.49 bowls, SD=5.10).The current research supports the use of personalized feedback as a useful intervention method to increase commitment to quit WP, but suggests more intensive interventions may be necessary to achieve WP cessation.

A FDG-PET/CT image feature with optimal prognostic potential for locally-advanced non-small cell lung cancer (LA-NSCLC) patients has yet to be identified, and neither has the optimal time for FDG-PET/CT response assessment; furthermore, nodal features have been largely ignored in the literature. We propose to identify image features or imaging time point with maximal prognostic power.Consecutive consenting patients with LA-NSCLC receiving curative intent CRT were enrolled. 4DPET/4DCT scans were acquired 0, 2, 4, and 7 weeks during IMRT treatment. Eleven image features and their rates of change were recorded for each time point and tested for each of the possible outcome 2 years post CRT using the Kaplan-Meier method.32 consecutive patients were recruited, 27 completing all scans. Restricting analysis to 4DPET/4DCT features and rates of change with p 0.005, several volume-based features and their rates of change reached significance. Image features involving nodal disease were the only ones associated with overall survival.Several 4DPET/CT features and rates of change can reach significant association (p 0.005) with outcomes, including overall survival, at many time points. The optimal time for adaptive CRT is therefore not constrained uniquely on imaging.

We investigated how the visibility of targets influenced the type of point used to provide directions. In Study 1, we asked 605 passersby in three localities for directions to well-known local landmarks. When that landmark was in plain view behind the requester, most respondents pointed with their index fingers, and few respondents pointed more than once. In contrast, when the landmark was not in view, respondents pointed initially with their index fingers, but often elaborated with a whole-hand point. In Study 2, we covertly filmed the responses from 157 passersby we approached for directions, capturing both verbal and gestural responses. As in Study 1, few respondents produced more than one gesture when the target was in plain view and initial points were most likely to be index finger points. Thus, in a Western geographical context in which pointing with the index finger is the dominant form of pointing, a slight change in circumstances elicited a preference for pointing with the whole hand when it was the second or third manual gesture in a sequence.

IMPACT: This research suggests that African American and Latinx smokers who bear a disproportionate burden of tobacco-related harms are able to switch to e-cigarettes that present reduced harm to the user due to their similar reinforcement profile to cigarettes. OBJECTIVES/GOALS: Complete switching from combustible to electronic cigarettes (ECs) reduces harm to the user. For ECs to be a viable substitute, they need to be rewarding enough for regular use, indicated by factors such as craving and dependence (reinforcement value). Little is known about short-term changes in reinforcement value across trajectories of EC use. METHODS/STUDY POPULATION: Participants were randomized 2:1 to switch to a nicotine salt pod system EC or continue smoking (assessment-only control) in a 6-week trial. 114 African American (n=60) and Latinx (n=54) smokers were randomized to receive ECs and are included in the current investigation. At week 6, participants were classified by use trajectory: exclusive smokers (n=16), exclusive EC users (n=32), or dual users (n=66). Participants reported on their EC, cigarette, and total nicotine dependence (cigarette + EC dependence), cigarette and EC use, and nicotine craving and withdrawal at baseline and week 6. Cotinine and exhaled carbon monoxide were assessed at baseline and week 6. RESULTS/ANTICIPATED RESULTS: Participants who completely switched from smoking to ECs (exclusive EC users) and those that partially switched (dual users), maintained cotinine levels (ps>.05) and showed reductions in cigarette dependence and withdrawal (ps

IntroductionThe present study examined how the lack of characterising flavours and low levels of humectants may affect users’ waterpipe tobacco (WT) smoking topography, subjective effects, toxicant exposure and intentions for continued use.Methods89 WT smokers completed four ad libitum smoking sessions (characterising flavor/high humectant (+F+H); characterising flavor/low humectant (+F-H); no characterising flavor/high humectant (-F+H); no characterising flavor/low humectant (-F-H)) in a randomised cross-over design. WT was commercially available; same brand but nicotine levels were not held constant. A subsample (n=50) completed a standardised, 10-puff session preceding ad libitum smoking. Participants completed questionnaires, exhaled carbon monoxide (eCO) testing and provided blood samples for plasma nicotine. Smoking topography was measured throughout the session. Post hoc analyses showed that -F+H and -F-H did not differ significantly in humectant levels. Therefore, these groups were collapsed in analyses (-F-H).ResultsWT smokers reported significantly greater satisfaction, liking, enjoyment and greater intentions for continued use when smoking +F+H compared with other WT products, with -F-H receiving the lowest ratings. Significant differences in topography were observed during standardised and ad libitum sessions, with the -F-H preparation leading to greater total inhaled volume and eCO boost, but lower nicotine boost compared with +F+H (all pDiscussionThe findings demonstrate the importance of flavours and humectants on improving WT smoking experience and increasing the likelihood that users will want to initiate and continue smoking. Moreover, it demonstrates that flavours and humectants influence smoking behaviour and toxicant exposure in some unexpected ways that are important for regulatory efforts.

Poor sleep health is associated with numerous health concerns, and sleep problems are exacerbated by cigarette smoking. Although rates of traditional tobacco use are declining, rates of electronic cigarette (e-cigarette) use are comparatively high and growing. Given that nicotine is a primary mechanism by which smoking negatively impacts sleep health, e-cigarette use may also be linked to poor sleep health; however, no research has investigated this association. Participants were 1,664 college students, 40.9% of whom reported ever trying or currently using an e-cigarette. Questionnaires assessed demographic information, sleep health and e-cigarette use status and patterns. All measures were completed remotely via a secure online survey. Analysis of covariance was used to compare the sleep health of daily/non-daily e-cigarette users to (a) non-users and (b) users of combustible cigarettes. Gender and drinks per week were included as covariates in analyses. Current combustible and e-cigarette users reported significantly more sleep difficulties than never users. Users of e-cigarettes reported greater use of sleep medication than combustible cigarette users. Similar to combustible cigarette smoking, e-cigarette use (vs. non-use) was associated with worse sleep health, even among non-daily e-cigarette users. These findings may indicate a need for assessment of and education on the role of e-cigarette use in sleep health among individuals who report experimentation with or current use of e-cigarettes. Future research should examine these relationships prospectively.

The current study examined changes in prevalence of e-cigarette use and perceptions of the harmfulness of e-cigarette and combustible cigarettes following a campus-wide tobacco ban. Undergraduate students completed surveys of tobacco use and perceived product harmfulness. Four samples were collected: in 2013 prior to the ban (n = 792) and in fall 2014 (n = 310), 2015 (n = 208), and 2016 (n = 417). E-cigarette use increased in the years following the ban (p = .01) while combustible cigarette use decreased from 2013 to 2016 (p = .02). Men were more likely than women to use both products (ps < .05). Students’ perceptions of the harmfulness of combustible and electronic cigarettes remained stable in the years following the ban (p > .05). This study is the first to examine the impact of including e-cigarettes in tobacco free policies. Combustible cigarette use declined, but e-cigarette use increased in the years following the e-cigarette ban. Prospective research is needed to understand the long-term impacts of e-cigarette bans.

Suicide is the second leading cause of death for American Indian (AI) young adults. Alcohol use is a well-established risk factor for suicide. On average, AIs ages 12 to 20 exhibit the second-highest rate of binge drinking compared to all other ethnic groups. The current study investigated the relation between alcohol use and suicide ideation in an AI sample and examined these relations in the context of the interpersonal theory of suicide (ITS). It was hypothesized that perceived burdensomeness and thwarted belongingness would each significantly moderate the relations between alcohol use and suicide ideation in an AI sample. College students who self-identified as American Indian (

Follicular porokeratosis is a rare variant of porokeratosis in which the coronoid lamellae are confined to hair follicles. It classically presents with annular plaques with a surrounding keratotic ridge. However, the clinical presentation has shown significant variation in reported cases. We present the case of a 26-year-old man with chronic diffuse follicular spicules associated with alopecia. Clinical findings were suggestive of trichodysplasia spinulosa, but multiple biopsies showed findings consistent with follicular porokeratosis. Diffusely spiculated presentation as present in our patient has not been previously reported in the literature. It is important to recognize the necessity of histopathologic confirmation in a diagnostically challenging condition such as follicular porokeratosis.

Purpose The use of electronic cigarettes (e-cigarettes) has risen dramatically in recent years. However, there are currently no published data on the use of e-cigarettes among cardiac patients. The current study reports on the prevalence, reasons for use, and perceived risks of e-cigarettes among patients with post-acute coronary syndrome (ACS). The relationship between e-cigarette use and post-ACS tobacco smoking cessation is also explored. Methods Participants were drawn from a randomized trial of smoking cessation treatments following hospitalization for ACS. The current study focused on 49 participants who completed e-cigarette questions at 24 weeks post-ACS. Results Of the 49 of participants, 51.0% reported ever use of an e-cigarette and 26.5% reported using an e-cigarette at some time during the 24 weeks post-ACS. Ever use and post-ACS use were both significantly associated with lower rates of abstinence from tobacco cigarettes. Participants perceived e-cigarettes as less harmful to cardiac health than tobacco use and Chantix (varenicline), and similarly harmful as nicotine replacement therapy. Participant perceived likelihood of experiencing a heart attack in the next year was 34.6% if they were to regularly use only e-cigarettes, significantly lower than the perceived risk of recurrence if they were to regularly smoke only tobacco cigarettes (56.2%) and significantly higher than the perceived risk of recurrence if they were to use no nicotine (15.2%). Conclusions A significant minority of patients are using e-cigarettes post-ACS. Providers should be prepared to discuss potential discrepancies between patient beliefs about the safety of e-cigarettes and the current state of the science.

Background Personalized normative alcohol feedback (PNF) is associated with decreased alcohol use among young adults. However, limited research has examined the influence of depressive symptoms on PNF efficacy. This study examined symptoms of depression as a moderator of college student response to a computerized PNF intervention for alcohol use. Methods College students (N = 212, 59% female) who reported drinking in a typical week completed baseline and one-month assessments as part of a previously published intervention trial. We randomized participants to alcohol PNF (n = 153) or assessment only (n = 59). We used regression models to examine the interaction between PNF and symptoms of depression on alcohol outcomes at one-month follow-up. Results One in four participants screened positive for clinically significant symptoms of depression. Depressive symptoms did not moderate intervention effects on drinking quantity. However, PNF was only associated with reduced frequency of heavy episodic drinking and lower probability of any alcohol-related consequence in the context of mild to moderate (not minimal) symptoms of depression. Conclusions PNF is more effective than assessment alone in reducing drinking quantity, regardless of symptoms of depression. However, it may only be more effective in decreasing frequency of heavy episodic drinking and the probability of alcohol-related consequences among those experiencing mild to moderate (as opposed to minimal) symptoms of depression. Alcohol intervention trials should assess symptoms of depression and consider them in data analysis.

Nocardia is a ubiquitous environmental pathogen that causes infection primarily following inhalation into the lungs. It is generally thought to cause infection primarily in immunocompromised patients, but nonimmunocompromised individuals are also at risk of infection. We sought to compare risk factors, clinical manifestations, diagnostic approach, treatment, and mortality in immunocompromised and nonimmunocompromised adults with nocardiosis. We studied all adults with culture-proven Nocardia infection at a tertiary care hospital from 1994 to 2015 and compared immunocompromised with nonimmunocompromised patients. The immunocompromised group included patients who had a solid organ transplant, hematopoietic cell transplant (HCT), hematological or solid tumor malignancy treated with chemotherapy in the preceding 90 days, inherited immunodeficiency, autoimmune/inflammatory disorders treated with immunosuppressive agents, or high-dose corticosteroid therapy for at least 3 weeks before the diagnosis of nocardiosis. There were 112 patients, mean age 55 ± 17 years; 54 (48%) were women. Sixty-seven (60%) were immunocompromised, and 45 (40%) were nonimmunocompromised. The lung was the site of infection in 54 (81%) immunocompromised and 25 (55%) nonimmunocompromised patients. Pulmonary nocardiosis in immunocompromised patients was associated with high-dose corticosteroids, P = .002 and allogeneic HCT, P = .01, and in nonimmunocompromised patients with cigarette smoking, bronchiectasis, and other chronic lung diseases, P = .002. Cavitation occurred only in the immunocompromised group, P

Object-oriented (OO) programs, which use subtyping and dynamic dispatch, make specification and verification difficult because the code executed by a method call may dynamically be dispatched to an overriding method in any subtype, even ones that did not exist at the time the program was specified. Modular reasoning for such programs means allowing one to add new subtypes to a program without re-specifying and re-verifying it. In a 2015 ACM TOPLAS paper we presented a model-theoretic characterization of a Hoare-style modular verification technique for sequential OO programs called “supertype abstraction,” defined behavioral subtyping, and proved that behavioral subtyping is both necessary and sufficient for the validity of supertype abstraction. The present paper is aimed at graduate students and other researchers interested in formal methods and gives a comprehensive overview of our prior work, along with the motivation and intuition for that work, with examples.

As a result of its presence in water as a volatile disinfection byproduct, bromodichloromethane (BDCM), which is mutagenic, poses a potential health risk from exposure via oral, dermal and inhalation routes. We developed a refined human physiologically based pharmacokinetic (PBPK) model for BDCM (including new chemical-specific human parameters) to evaluate the impact of BDCM exposure during showering and bathing on important measures of internal dose compared with oral exposure. The refined model adequately predicted data from the published literature for oral, dermal and bathing/showering exposures. A liter equivalency approach (L-eq) was used to estimate BDCM concentration in a liter of water consumed by the oral route that would be required to produce the same internal dose of BDCM resulting from a 20-min bath or a 10-min shower in water containing 10 µg l(-1) BDCM. The oral liter equivalent concentrations for the bathing scenario were 605, 803 and 5 µg l(-1) BDCM for maximum venous blood concentration (Cmax), the area under the curve (AUCv) and the amount metabolized in the liver per hour (MBDCM), respectively. For a 10-min showering exposure, the oral L-eq concentrations were 282, 312 and 2.1 µg l(-1) for Cmax, AUC and MBDCM, respectively. These results demonstrate large contributions of dermal and inhalation exposure routes to the internal dose of parent chemical reaching the systemic circulation, which could be transformed to mutagenic metabolites in extrahepatic target tissues. Thus, consideration of the contribution of multiple routes of exposure when evaluating risks from water-borne BDCM is needed, and this refined human model will facilitate improved assessment of internal doses from real-world exposures. Published 2015. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Compositional reuse of software libraries is important for productivity. To promote reliability and correctness, there must also be a way to compose specifications for reuse. However, specifications cannot be adapted by the use of wrappers in the same ways as code, which leads to specifications being copied and modified. This copying and modification of specifications leads to poor maintainability and technical debt. We propose a system, Spekl, that solves these problems and makes compositional reuse of specifications possible in a way independent of the choice of specification languages and tools. We provide a detailed description of our system as well as provide details on our domain specific language for creating new tools, provide details on how to author new specifications, and demonstrate how Spekl facilitates compositional reuse through specification layering.

In this paper, a novel steganography algorithm based on an improved "Matrix Pattern" (MP) method is presented. In this process, firstly, an RGB image is divided into the non-overlapping square-sized blocks. Next, 95 dynamicsized unique matrix patterns are automatically generated using the 4th and 5th bit layers of the green layer of each block, which are assigned to 95 English keyboard characters. Then, the blue layer of each block is used for embedding secret messages by adding matrix patterns which are assigned to the characters of the secret message. The results show that this algorithm has a high resistance against steganalysis attacks, including Regular Singular (RS), Sample Pair (SP), and PVD based attacks. Furthermore, the proposed algorithm not only improves capacity by over 27% when compared to the existing method, but also results in a slightly better transparency of the stego-image.

The availability of respiratory synchronized PET (4DPET) imaging has enabled more accurate analysis of metabolic response since motion blur is minimized. We present our preliminary analysis of serial FDG 4DPET images acquired at weeks 0, 2, 4, and 7 during radiotherapy of seven stage II–IIINSCLC patients. The tumor and nodal PTV of the week 0 images restrained a 4DPET image thresholding algorithm to automatically contour SUV levels ranging from 20 to 80% of the maximum SUV, creating an intensity volume histogram (IVH) for each week. These contours allowed analysis of PET volumes and standard PET metrics such as SUVmax and SUVmean. We found a trend for decreasing SUVmax and SUVmean over a treatment course in both the tumor and nodal regions. On average, the SUVmax within the tumor decreased by 17±13% (1 SD) after 2 weeks, 30±13% after 4 weeks, and 39±19% after 7 weeks of radiotherapy. Decreasing volume trends were also observed in the 20 to 80% max SUV autocontours, ranging from 26±29% to 50±40% respectively, over 7 weeks of treatment. Only one patient demonstrated an increase in FDG uptake within the tumor volume between week 0 and week 2 of treatment, and was also the only patient to recur locally at 3 months following treatment. Changes in tumor metabolism over the course of advanced NSCLCradiotherapy are quantifiable with serial FDG 4DPET imaging. Preliminary analysis suggests that variations in these trends could be useful in identifying non‐responding patients that may require an alternative radiotherapeutic approach.

This panel is comprised of current and prior student chapter officers, who will be discussing five selected themes influencing the success of Human Factors and Ergonomics Society (HFES) student chapters. These themes include: 1) administrative support, 2) chapter branding and funds, 3) chapter collaboration, 4) social activities, and 5) educational activities for chapters. We believe that these five pillars are necessary in providing a solid foundation for a successful and engaged chapter. Within each section, we discuss challenges and successes that our chapters have experienced. Additionally, we end with recommendations and suggestions that we hope other student chapters – HFES and otherwise – can use to bolster their group. We hope that these recommendations can foster the future success of aspiring Human Factors and Ergonomics Society student chapters.

It has been recognized that families of children with life-limiting health conditions struggle with significant financial demands, yet may not have awareness of resources available to them. Additionally, health care providers may not be aware of the socioeconomic needs of families they care for. This article describes a mixed-methods study examining the content validity and utility for health care providers of a poverty screening tool and companion resource guide for the pediatric palliative care population. The study found high relevance and validity of the tool. Significant barriers to implementing the screening tool in clinical practice were described by participants, including: concerns regarding time required, roles and responsibilities, and discomfort in asking about income. Implications for practice and suggestions for improving the tool are discussed. Screening and attention to the social determinants of health lie within the scope of practice of all health care providers. Social workers can play a leadership role in this work.

Using mass spectrometry to detect enzymatic activity offers several advantages over fluorescence-based methods. Automation of sample handling and analysis using platforms such as the RapidFire (Agilent Technologies, Lexington, MA) has made these assays amenable to medium-throughput screening (of the order of 100,000 wells). However, true high-throughput screens (HTS) of large compound collections (1 million) are still considered too time-consuming to be feasible. Here we propose a simple multiplexing strategy that can be used to increase the throughput of RapidFire, making it viable for HTS. The method relies on the ability to analyze pooled samples from several reactions simultaneously and to deconvolute their origin using "mass-tagged" substrates. Using the JmjD2d H3K9me3 demethylase as a model system, we demonstrate the practicality of this method to achieve a 4-fold increase in throughput. This was achieved without any loss of assay quality. This multiplex strategy could easily be scaled to give even greater reductions in analysis time.

This study was designed to empirically examine equipment and system monitoring task features of the new Multi-Attribute Task Battery-I I (MATB-II) and the original version (MATB). It also was intended to examine the effects of adaptive task allocation on system monitoring performance, as found in previous studies. In addition, two different computer displays (CRT and LCD) were used to test performance differences between the two systems in order to add historical fidelity to the study results. Sixty participants were randomly assigned to one of four experimental groups (MATB or MATB-II both on CRT or LCD), all receiving a return to manual control of the system monitoring task at mid experiment. A fifth group using the MATB on CRT with no task allocation was the control. Measures used to compare the two systems included percent of automation failures detected by participants in the system monitoring task and subjective workload. Results failed to show significance for the adaptive task allocation manipulation. However, significant differences in monitoring performance were found between the two systems. Implications for design of display and equipment features and future research are discussed.

While driver distraction has become one of the most studied topics in safety and in human factors, the focus has remained on the traditional elements of driver distraction. In this study, we manipulated the difficulty level of riddles to determine whether the cognitive processing associated with solving them would affect driving performance. Twenty-eight participants completed a series of eighteen short drives while undistracted or listening to a hard or easy riddles. Frequency of pressing the brake pedal, deviation in lane position, and average speed were analyzed. The results indicated that there was a main effect of riddle difficulty on how often the brake pedal was pressed. No main effects of measures on speed maintenance and lane position were found. While these results indicate there may be some differences related to difficulty of solving a problem while driving, further work is required to better quantify the effect. Keywords: Driver distraction; Language: en

Electronic cigarettes' (e-cigarettes) viability as a public health strategy to end smoking will likely be determined by their ability to mimic the pharmacokinetic profile of a cigarette while also exposing users to significantly lower levels of harmful/potentially harmful constituents (HPHCs). The present study examined the nicotine delivery profile of third- (G3) versus second-generation (G2) e-cigarette devices and their users' exposure to nicotine and select HPHCs compared with cigarette smokers.30 participants (10 smokers, 9 G2 and 11 G3 users) completed baseline questionnaires and provided exhaled carbon monoxide (eCO), saliva and urine samples. Following a 12-hour nicotine abstinence, G2 and G3 users completed a 2-hour vaping session (ie, 5 min, 10-puff bout followed by ad libitum puffing for 115 min). Blood samples, subjective effects, device characteristics and e-liquid consumption were assessed.Smokers, G2 and G3 users had similar baseline levels of cotinine, but smokers had 4 and 7 times higher levels of eCO (p0.0001) and total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (i.e., NNAL, p0.01), respectively, than G2 or G3 users. Compared with G2s, G3 devices delivered significantly higher power to the atomiser, but G3 users vaped e-cigarette liquids with significantly lower nicotine concentrations. During the vaping session, G3 users achieved significantly higher plasma nicotine concentrations than G2 users following the first 10 puffs (17.5 vs 7.3 ng/mL, respectively) and at 25 and 40 min of ad libitum use. G3 users consumed significantly more e-liquid than G2 users. Vaping urges/withdrawal were reduced following 10 puffs, with no significant differences between device groups.Under normal use conditions, both G2 and G3 devices deliver cigarette-like amounts of nicotine, but G3 devices matched the amount and speed of nicotine delivery of a conventional cigarette. Compared with cigarettes, G2 and G3 e-cigarettes resulted in significantly lower levels of exposure to a potent lung carcinogen and cardiovascular toxicant. These findings have significant implications for understanding the addiction potential of these devices and their viability/suitability as aids to smoking cessation.

Background and aims Concurrent alcohol use and waterpipe (WP) smoking is common among young adults. WP smokers are more than twice as likely to use alcohol as non-users and frequently consume alcohol immediately before and during a WP smoking session. It is unclear what impact alcohol has on WP smoking patterns and resultant exposure to tobacco-related toxicants. The current research aimed to understand the association between alcohol consumption and WP smoke exposure among WP lounge patrons. Methods Seventy-one lounge patrons (66.2% male; M age = 27.03, SD = 5.32) completed pre- and post-WP session self-report measures and biomarkers of smoking (expired carbon monoxide; eCO) and alcohol consumption (breath alcohol concentration; BrAC) upon entering and exiting the WP lounge. Results After controlling for number of bowls and charcoals smoked, greater consumption of alcohol was associated with greater smoke exposure among WP lounge patrons ( p Conclusions Concurrent alcohol use resulted in greater eCO, likley due to participants spending a greater amount of time in the WP lounge and experiencing longer sustained exposure to secondhand smoke. These findings illustrate a need for further research on the impact of alcohol consumption on WP smoking to assess the potential need for regulation of these products in WP lounges.

IntroductionOne possible reason for the rapid proliferation of waterpipe (WP) smoking is the pervasive use of flavoured WP tobacco. To begin to understand the impact of WP tobacco flavours, the current study examined the impact of a preferred WP tobacco flavour compared with a non-preferred tobacco flavoured control on user’s smoking behaviour, toxicant exposure and subjective smoking experience.MethodThirty-six current WP smokers completed two, 45-minute ad libitum smoking sessions (preferred flavour vs non-preferred tobacco flavour control) in a randomised cross-over design. Participants completed survey questionnaires assessing subjective smoking experience, exhaled carbon monoxide (eCO) testing, and provided blood samples for monitoring plasma nicotine. WP smoking topography was measured continuously throughout the smoking session.ResultsWhile participants reported an enhanced subjective smoking experience including greater interest in continued use, greater pleasure derived from smoking, increased liking and enjoyment, and willingness to continue use after smoking their preferred WP tobacco flavour (p values DiscussionThe current study is the first to examine flavours in WP smoking by measuring preferred versus control preparations to understand the impact on subjective experience, smoking behaviour and toxicant exposure. The pattern of results suggests that even this relatively minor manipulation resulted in significant changes in subjective experience. These results indicate a possible need for regulations restricting flavours in WP tobacco as with combustible cigarettes.