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A scale model of a 2-car metro train on a slab track rail viaduct was employed to investigate the reduction of in-car and wayside noise when acoustic treatments were added to the inside face of the edge noise barrier and within the four-foot. The performance of the acoustic treatments was evaluated in full octaves for the full-scale frequency range of 31.5 Hz to 2 kHz. The scale model results were compared with general rail noise modelling prediction formulae and with numerical modelling results using ODEON. The model results confirmed that the interior noise level experienced by passengers is likely to increase with the addition of viaduct edge noise barriers and that wayside noise levels are reduced due to the noise barrier effect. With the addition of acoustic panels on the inside face of the viaduct edge barrier and within the four-foot, in-car and wayside noise levels reduce.

Aim Delirium is common and dangerous among elderly inpatients; yet, it is underdiagnosed and thus undertreated. This study aimed to test the diagnostic characteristics of a noninvasive point-of-care device with two-channel (bispectral) electroencephalography (EEG) for the screening of delirium in the hospital. Methods Patients admitted to the University of Iowa Hospitals and Clinics were assessed for the presence of delirium with a clinical assessment, the Confusion Assessment Method for Intensive Care Unit and Delirium Rating Scale. Subsequently, we obtained a 10-min bispectral EEG (BSEEG) recording from a hand-held electroencephalogram device during hospitalization. We performed power spectral density analysis to differentiate between those patients with and without delirium. Results Initially 45 subjects were used as a test dataset to establish a cut-off. The BSEEG index was determined to be a significant indicator of delirium, with sensitivity 80% and specificity 87.7%. An additional independent validation dataset with 24 patients confirmed the validity of the approach, with a sensitivity of 83.3% and specificity of 83.3%. Conclusion In this pilot study, the BSEEG method was able to distinguish delirious patients from non-delirious patients. Our data showed the feasibility of this technology for mass screening of delirium in the hospital.

The unprecedented growth of demand for charging electric vehicles (EVs) calls for novel expansion solutions to today's charging networks. Riding on the wave of the proliferation of sharing economy, Airbnb-like charger sharing markets opens the opportunity to expand the existing charging networks without requiring costly and time-consuming infrastructure investments, yet the successful design of such markets relies on innovations at the interface between game theory, mechanism design, and large scale optimization. In this paper, we propose a price-based iterative double auction for charger sharing markets where charger owners rent out their under-utilized chargers to the charge-needing EV drivers. Charger owners and EV drivers form a two-sided market which is cleared by a price-based double auction. Chargers' locations, availability, and time unit costs as well as the EV drivers' time, distance constraints, and preferences are considered in the allocation and scheduling process. The goal is to compute social welfare maximizing allocations which benefits both charger owners and EV drivers and, in turn, ensure the continuous growth of the market. We prove that the proposed double auction is budget balanced, individually rational, and that it is a weakly dominant strategy for EV drivers and charger owners to truthfully report their charging time constraints. In addition, results from our computation study show that the double auction achieves on average 94% efficiency compared with the optimal solutions and scales well to larger problem instances.

Background Oral chlorhexidine prophylaxis can decrease occurrence of ventilator-associated pneumonia. However, the importance of timing has never been fully explored. Objective To see if early administration of oral chlorhexidine is associated with lower incidence of early ventilator-associated pneumonia (within 5 days of admission to intensive care unit) in intubated air ambulance patients. Methods A single-center, retrospective cohort study of intubated adults transported by a university-based air ambulance service and admitted to a surgical intensive care unit from July 2011 through April 2013. Primary exposure was time from helicopter retrieval to the first dose of oral chlorhexidine in the intensive care unit. Early chlorhexidine was defined as receipt of the drug within 6 hours of helicopter departure. The primary outcome was clinical diagnosis of early ventilator-associated pneumonia. Patients who were less than 18 years old, died within 72 hours of admission, or had pneumonia at admission were excluded. Results Among 134 patients, 49% were treated with chlorhexidine before 6 hours, 84% were treated before 12 hours, and 11% were treated for early pneumonia. Early chlorhexidine (before 6 hours; 15%) was not associated (P = .21) with early pneumonia (8%). Furthermore, median times to chlorhexidine did not differ significantly (P = .23) between patients in whom pneumonia developed (5.2 hours) and patients with no pneumonia (6.1 hours). Conclusions Early administration of oral chlorhexidine in intubated patients was not associated with a reduction in the incidence of ventilator-associated pneumonia in a surgical intensive care unit with high rates of chlorhexidine administration before 12 hours.

Purpose Rural emergency department (ED) patients require interhospital transfer for definitive care at nearly 6 times the national rate, yet transfer decision-making is variable. The goal of this study was to understand patient experiences, preferences, and decision-making in the rural interhospital transfer process, and to measure the concordance between patient opinions and provider perceptions. Methods Ours is a mixed methods study of patients transferred to a 711-bed Midwestern academic medical center and the emergency physicians in community hospitals. Qualitative interviews were conducted by a single research assistant with admitted patients transferred from an ED, and a corresponding survey was distributed to community emergency physicians. Standardized scenarios were posed to both groups to understand transfer priorities. Findings Seventy-nine patients and 40 physicians participated in this study. Patients and physicians cited proximity to home, medical expertise, a personal relationship with a health care provider, health insurance, privacy concerns, and patient choice as the primary factors that influenced patient transfer priorities. Compared with patient respondents, physicians overestimated the patient-perceived importance of proximity to home (P = .015) and being cared for by a personal physician (P = .049), but they underestimated the value of receiving treatment in a comprehensive medical center (P = .002). In standardized scenarios, physicians agreed with patients in transfer preferences for conditions requiring neurosurgical consultation, but they underestimated patients’ desire for transfer for pneumonia requiring mechanical ventilation. Conclusion Patients and physicians recognize similar factors that influence patient preferences in interhospital ED transfer, but physicians may overestimate the value of nonmedical influences on decision-making priorities.

Purpose The purposes of the study are to describe current practice of ventilation in a modern air medical system and to measure the association of ventilation strategy with subsequent ventilator care and acute respiratory distress syndrome (ARDS). Materials and methods Retrospective observational cohort study of intubated adult patients (n = 235) transported by a university-affiliated air medical transport service to a 711-bed tertiary academic center between July 2011 and May 2013. Low tidal volume ventilation was defined as tidal volumes less than or equal to 8 mL/kg predicted body weight. Multivariable regression was used to measure the association between prehospital tidal volume, hospital ventilation strategy, and ARDS. Results Most patients (57%) were ventilated solely with bag valve ventilation during transport. Mean tidal volume of mechanically ventilated patients was 8.6 mL/kg predicted body weight (SD, 0.2 mL/kg). Low tidal volume ventilation was used in 13% of patients. Patients receiving low tidal volume ventilation during air medical transport were more likely to receive low tidal volume ventilation in the emergency department ( P P = .015). Acute respiratory distress syndrome was not associated with prehospital tidal volume ( P = .840). Conclusions Low tidal volume ventilation was rare during air medical transport. Air transport ventilation strategy influenced subsequent ventilation but was not associated with ARDS.

Introduction: HIV and syphilis testing rates remain low among men who have sex with men (MSM) in low- and middle-income countries (LMICs). Community engagement has been increasingly used to promote HIV testing among key populations in high-income countries, often in settings with stronger civil society. This study aimed to assess socio-demographic, behavioural, and community engagement factors associated with HIV and syphilis testing among MSM in China. Methods: MSM ≥16 years old who had condomless sex in the past three months were recruited nationwide to complete a cross-sectional online survey in November 2015. Data were collected on socio-demographics, sexual behaviours, HIV testing, syphilis testing, and community engagement in sexual health. We defined community engagement in sexual health using six items assessing awareness and advocacy of sexual health programmes. The underlying factor structure of a 6-item community engagement scale was determined through exploratory factor analysis. Univariate and multivariable logistic regressions identified correlates of HIV and syphilis testing. Results: 1189 MSM were recruited. 54% (647/1189) of men had ever tested for HIV and 30% (354/1189) had ever tested for syphilis. Factor analysis suggested three levels of community engagement (minimal, moderate, and substantial) and this model explained 79.5% of observed variance. A quarter (26%, 312/1189) reported none to minimal engagement, over one half (54%, 644/1189) reported moderate engagement, and a fifth (20%, 233/1189) reported substantial engagement. Multivariable logistic regression showed that MSM with greater community engagement in sexual health were more likely to have ever tested for HIV (substantial vs. no engagement: aOR 7.91, 95% CI 4.98–12.57) and for syphilis (substantial vs. no engagement: aOR 5.35, 95% CI 3.16–9.04). Conclusions: HIV and syphilis testing are suboptimal among MSM in China. Community engagement may be useful for promoting testing in China and should be considered in intervention development and delivery. Further research is needed to better understand the role of LMIC community engagement in HIV interventions.

Background: Many men who have sex with men (MSM) in China are “in the closet.” The low rate of disclosure may impact sexual behaviours, testing for HIV and other sexually transmitted infections (STIs), and diseases transmission. This study examines factors associated with overall sexual orientation disclosure and disclosure to healthcare professionals. Methods: A nationwide cross-sectional online survey was conducted from September 2014 to October 2014 in China. Participants completed questions covering socio-demographic information, sexual behaviours, HIV/STI testing history, and self-reported HIV status. We defined healthcare professional disclosure as disclosing to a doctor or other medical provider. Results: A total of 1819 men started the survey and 1424 (78.3%) completed it. Among the 1424 participants, 62.2% (886/1424) reported overall disclosure, and 16.3% (232/1424) disclosed to healthcare professionals. In multivariate analyses, the odds of sexual orientation disclosure were 56% higher among MSM who used smartphone-based, sex-seeking applications [adjusted odds ratio (aOR) = 1.56, 95% CI: 1.25–2.95], but were lower among MSM reporting sex while drunk or recreational drug use. The odds of disclosure to a healthcare professional were greater among MSM who had ever tested for HIV or STIs (aOR = 3.36, 95% CI: 2.50–4.51 for HIV, and aOR = 4.92, 95% CI: 3.47–6.96 for STIs, respectively) or self-reported as living with HIV (aOR = 1.59, 95% CI: 0.93–2.72). Conclusion: Over 80% of MSM had not disclosed their sexual orientation to health professionals. This low level of disclosure likely represents a major obstacle to serving the unique needs of MSM in clinical settings. Further research and interventions to facilitate MSM sexual orientation disclosure, especially to health professionals, are urgently needed.

Introduction: HIV and syphilis testing rates remain low among men who have sex with men (MSM) in low- and middle-income countries (LMICs). Community engagement has been increasingly used to promote HIV testing among key populations in high-income countries, often in settings with stronger civil society. This study aimed to assess socio-demographic, behavioural, and community engagement factors associated with HIV and syphilis testing among MSM in China.

Dietary fiber intake is linked to a reduced risk of colon cancer. This effect may in part be due to butyrate, the fermentation product of fiber in the colon. Butyrate is a short-chain fatty acid that acts as a histone deacetylase inhibitor (HDACi). Butyrate induces apoptosis and represses clonal growth of colorectal cancer (CRC) cells, in a manner dependent upon the hyperactivation of Wnt /beta-catenin signaling. While fiber has been linked to CRC prevention, in vitro studies on the action of butyrate have used CRC cell lines, instead of cells representative of earlier stages of colonic neoplasia, which are the likely target of butyrate-mediated preventive activity. The LT97 cell line is derived from a microadenoma, the earliest stage of colonic neoplasia from which cells can be isolated. We characterized LT97 cells with respect to effects of butyrate on Wnt signaling and apoptosis, and we determined whether modulation of CREB binding protein (CBP)/p300 activity influences the ability of butyrate to induce Wnt activity and apoptosis. We report that in LT97 cells, butyrate induces apoptosis, strongly upregulates Wnt signaling, and the upregulation of Wnt signaling is dependent upon CBP/p300 activity. In addition, findings from overexpression experiments suggest differences between CBP and p300 in their ability to influence Wnt signaling in LT97 cells; p300, but not CBP, stimulates basal Wnt activity. We also evaluated differences in gene expression between early stage LT97 cells and late stage metastatic SW620 CRC cells that exhibit markedly different cellular phenotypes. The comparative gene expression analyses revealed differences that may impact neoplastic progression and the sensitivity to the effects of butyrate. The findings have implications for the prevention of CRC by fiber/butyrate.

This paper presents a multiagent systems model for patient diagnostic services scheduling. We assume a decentralized environment in which patients are modeled as self-interested agents who behave strategically to advance their own benefits rather than the system wide performance. The objective is to improve the utilization of diagnostic imaging resources by coordinating patient individual preferences through automated negotiation. The negotiation process consists of two stages, namely patient selection and preference scheduling. The contract-net protocol and simulated annealing based meta-heuristics are used to design negotiation protocols at the two stages respectively. In terms of game theoretic properties, we show that the proposed protocols are individually rational and incentive compatible. The performance of the preference scheduling protocol is evaluated by a computational study. The average percentage gap analysis of various configurations of the protocol shows that the results obtained from the protocol are close to the optimal ones. In addition, we present the algorithmic properties of the preference scheduling protocol through the validation of a set of eight hypotheses.

This national survey study uses National Health and Nutrition Examination Survey (NHANES) data to estimate the prevalence of alcoholic fatty liver disease (AFLD) overall and with stage 2 or greater and stage 3 or greater fibrosis among US adults from 2001 to 2016.

Mutations in the WNT/beta-catenin pathway are responsible for initiating the majority of colorectal cancers (CRCs). We have previously shown that hyperactivation of this signaling by histone deacetylase inhibitors (HDACis) such as butyrate, a fermentation product of dietary fiber, promotes CRC cell apoptosis. The extent of association between beta-catenin and the transcriptional coactivator CREB-binding protein (CBP) influences WNT/catenin signaling and, therefore, colonic cell physiology. CBP functions as a histone acetylase (HAT); therefore, we hypothesized that the modulation of WNT/catenin activity by CBP modifies the ability of the HDACi butyrate to hyperinduce WNT signaling and apoptosis in CRC cells. Our findings indicate that CBP affects the hyperinduction of WNT activity by butyrate. ICG-001, which specifically blocks association between CBP and beta-catenin, abrogates the butyrate-triggered increase in the number of CRC cells with high levels of WNT/catenin signaling. Combination treatment of CRC cells with ICG-001 and butyrate results in cell type-specific effects on apoptosis. Further, both butyrate and ICG-001 repress CRC cell proliferation, with additive effects in suppressing cell growth. Our study strongly suggests that ICG-001-like agents would be effective against butyrate/HDACi-resistant CRC cells. Therefore, ICG-001-like agents may represent an important therapeutic option for CRCs that exhibit low-fold hyperactivation of WNT activity and apoptosis in the presence of HDACis. The findings generated from this study may lead to approaches that utilize modulation of CBP activity to facilitate CRC therapeutic or chemopreventive strategies.

Introduction Crowdsourcing has been used to spur innovation and increase community engagement in public health programmes. Crowdsourcing is the process of giving individual tasks to a large group, often involving open contests and enabled through multisectoral partnerships. Here we describe one crowdsourced video intervention in which a video promoting condom use is produced through an open contest. The aim of this study is to determine whether a crowdsourced intervention is as effective as a social marketing intervention in promoting condom use among high-risk men who have sex with men (MSM) and transgender male-to-female (TG) in China. Method We evaluate videos developed by crowdsourcing and social marketing. The crowdsourcing contest involved an open call for videos. Entries were judged on capacity to promote condom use, to be shareable or ‘go viral’ and to give value to the individual. 1170 participants will be recruited for the randomised controlled trial. Participants need to be MSM age 16 and over who have had condomless anal sex in the last 3 months. Recruitment will be through an online banner ad on a popular MSM web page and other social media platforms. After completing an initial survey, participants will be randomly assigned to view either the social marketing video or the crowdsourcing video. Follow-up surveys will be completed at 3 weeks and 3 months after initial intervention to evaluate condomless sex and related secondary outcomes. Secondary outcomes include condom social norms, condom negotiation, condom self-efficacy, HIV/syphilis testing, frequency of sex acts and incremental cost. Ethics and dissemination Approval was obtained from the ethical review boards of the Guangdong Provincial Center for Skin Diseases and STI Control, UNC and UCSF. The results of this trial will be made available through publication in peer-reviewed journals. Trial registration number NCT02516930.

Objectives In this study, we evaluate the diagnostic utility of a hybrid γ-camera-computer tomography (SPECT-CT) indium-111 (111-In)-capromab pendetide scan in detecting seminal vesicle invasion (SVI) in select patients evaluated for primary surgical treatment of prostate cancer (CaP). Methods and materials We retrospectively analyzed a prospective database of patients who underwent preoperative SPECT-CT imaging with 111-In-capromab-pendetide as part of a staging evaluation who were subsequently treated with radical surgery in our center. Only patients with clinically localized disease were included. We calculated diagnostic properties of the hybrid scan in detecting SVI compared with final pathology. Regression analyses were performed, including scan and preoperative variables to predict SVI. Results We retrieved 50 medical records matching our criteria. Median patient age was 61 years (range 45–74). Most patients had a clinical T1c CaP and biopsy Gleason score of 7 or higher. On final pathology, SVI was found in 12 (24%) specimens and radiotracer signal in the seminal vesicle region was reported in 15 (30%) imaging studies. Hybrid SPECT-CT imaging had a sensitivity of 25%, specificity of 61.9%, positive and negative predictive values of 20% and 74.3%, respectively, for detecting SVI. SPECT-CT results did not contribute significantly to SVI prediction on univariate (P = 0.627) or multivariate (P = 0.754) analyses. Conclusions SPECT-CT imaging with 111-In-capromab-pendetide is not reliable in detecting or excluding SVI in this select cohort. High rates of positive radiotracer signals from healthy seminal vesicles raise concerns regarding pharmacologic properties of this radiotracer molecule.

Next generation heterogeneous wireless networks are expected to interwork with Internet Protocol (IP)-based infrastructures. Conventional network services operate like silos in that a specific set of services are offered over a specific type of access network. It is desirable for users to be able to roam between fixed and mobile networks that employ different access technologies. Therefore, mobility management with quality of service (QoS) support is of particular importance and one of the driving forces of convergence. Since service providers often provide more than one service to their subscribers, it is important to facilitate convergence of network charging architecture through a common charging framework. One of the main issues of IP-based convergence is security and privacy. This requires coordination of different security policies in diverse networks that have different security levels and capabilities. The business case for migration to an IP-based platform motivates operators to deliver more powerful services for customers as well as a better user experience. This paper provides an overview of converged mobile Internet architectures and their implications on QoS, charging/billing and security, as well as emerging business models for telecommunication services.

Purpose: Clinical and 3D dosimetric parameters are associated with symptomatic radiation pneumonitis rates in retrospective studies. Such parameters include: mean lung dose (MLD), radiation (RT) dose to perfused lung (via SPECT), and pre-RT lung function. Based on prior publications, we defined pre-RT criteria hypothesized to be predictive for later development of pneumonitis. We herein prospectively test the predictive abilities of these dosimetric/functional parameters on 2 cohorts of patients from Duke and The Netherlands Cancer Institute (NKI). Methods and Materials: For the Duke cohort, 55 eligible patients treated between 1999 and 2005 on a prospective IRB-approved study to monitor RT-induced lung injury were analyzed. A similar group of patients treated at the NKI between 1996 and 2002 were identified. Patients believed to be at high and low risk for pneumonitis were defined based on: ( 1 ) MLD; ( 2 ) OpRP (sum of predicted perfusion reduction based on regional dose-response curve); and ( 3 ) pre-RT DLCO. All doses reflected tissue density heterogeneity. The rates of grade ≥2 pneumonitis in the "presumed" high and low risk groups were compared using Fisher's exact test. Results: In the Duke group, pneumonitis rates in patients prospectively deemed to be at "high" vs. "low" risk are 7 of 20 and 9 of 35, respectively; p = 0.33 one-tailed Fisher's. Similarly, comparable rates for the NKI group are 4 of 21 and 6 of 44, respectively, p = 0.41 one-tailed Fisher's. Conclusion: The prospective model appears unable to accurately segregate patients into high vs. low risk groups. However, considered retrospectively, these data are consistent with prior studies suggesting that dosimetric ( e.g. , MLD) and functional ( e.g. , PFTs or SPECT) parameters are predictive for RT-induced pneumonitis. Additional work is needed to better identify, and prospectively assess, predictors of RT-induced lung injury.

Nuclear factor-kappa B (NF-κB) is a ubiquitously expressed protein complex regulating the transcription of genes involved in inflammation and pain. Increased NF-κB activity in immune and nervous system cells is linked to several chronic pain conditions in humans as well as inflammation- and nerve injury-evoked pain in animals. A recent in vitro study further demonstrates that increased NF-κB activity in astrocytes decreases transcription of catechol-o-methyltransferase (COMT), an enzyme that inactivates catecholamines that cause pain. The purpose of the present study was to examine the relationship between systemic and astrocytic NF-κB activity, pain, and COMT expression in an animal model of inflammation. Results demonstrated that administration of the inflammatory stimulant complete Freund’s adjuvant (CFA) led to increased pain and decreased COMT protein expression in an NF-κB-dependent manner. Specifically, we found that rats and mice receiving intraplantar CFA exhibited increased behavioral responses to mechanical and thermal heat stimuli. CFA-evoked pain was blocked in rats receiving a pre-emptive systemic dose of the NF-κB inhibitor MG132 and exacerbated in IKKca mice with constitutive NF-κB activity in astrocytes. Furthermore, we observed NF-κB-linked reductions in COMT expression in midbrain at 6h and 1d following CFA in rats and at 1h and 1d in forebrain and midbrain following CFA in IKKca mice. Collectively, these results demonstrate that systemic and astrocytic NF-κB activity drive inflammatory pain and regulate the expression of COMT in forebrain and midbrain structures.

Background : Many men who have sex with men (MSM) in China are “ in the closet. ” The low rate of disclosure may impact sexual behaviours, testing for HIV and other sexually transmitted infections (STIs), and diseases transmission. This study examines factors associated with overall sexual orientation disclosure and disclosure to healthcare professionals. Methods : A nationwide cross-sectional online survey was conducted from September 2014 to October 2014 in China. Participants completed questions covering socio-demographic information, sexual behaviours, HIV/STI testing history, and self-reported HIV status. We defined healthcare professional disclosure as disclosing to a doctor or other medical provider. Results : A total of 1819 men started the survey and 1424 (78.3%) completed it. Among the 1424 participants, 62.2% (886/ 1424) reported overall disclosure, and 16.3% (232/1424) disclosed to healthcare professionals. In multivariate analyses, the odds of sexual orientation disclosure were 56% higher among MSM who used smartphone-based, sex-seeking applications [adjusted odds ratio (aOR) = 1.56, 95% CI: 1.25 – 2.95], but were lower among MSM reporting sex while drunk or recreational drug use. The odds of disclosure to a healthcare professional were greater among MSM who had ever tested for HIV or STIs (aOR = 3.36, 95% CI: 2.50 – 4.51 for HIV, and aOR = 4.92, 95% CI: 3.47 – 6.96 for STIs, respectively) or self-reported as living with HIV (aOR = 1.59, 95% CI: 0.93 – 2.72). Conclusion : Over 80% of MSM had not disclosed their sexual orientation to health professionals. This low level of disclosure likely represents a major obstacle to serving the unique needs of MSM in clinical settings. Further research and interventions to facilitate MSM sexual orientation disclosure, especially to health professionals, are urgently needed. Keywords: China; disclosure; healthcare professional; men who have sex with men (MSM); sexual behaviours; sexual orientation (Published: 6 February 2017) Tang W et al. Journal of the International AIDS Society 2017, 20: 21416 http://www.jiasociety.org/index.php/jias/article/view/21416 | http://dx.doi.org/10.7448/IAS.20.1.21416

Deregulated WNT/catenin pathway, usually resulting from mutations in the adenomatous polyposis coli and beta-catenin genes, drives colorectal tumorigenesis. Dietary fiber has been shown to have a protective role against colorectal cancer (CRC). We have previously demonstrated that the histone deacetylase inhibitor (HDACi) butyrate, a fermentation product of dietary fiber, induces WNT/catenin hyperactivation, which promotes CRC cell apoptosis. Therefore, the ability of butyrate to induce WNT hyperactivation and thus promote CRC cell apoptosis may in part explain the preventive function of fiber against CRC. The association between beta-catenin and the transcriptional coactivator p300 may influence WNT/catenin signaling and, therefore, colonic cell physiology. p300 functions as a histone acetylase (HAT); therefore, the modulation of WNT/catenin activity by p300 may influence the ability of the HDACi butyrate to hyperinduce WNT signaling and apoptosis in CRC cells. Our findings indicate that p300 affects the hyperinduction of WNT activity by butyrate. Knockdown of p300 levels represses butyrate-mediated WNT/catenin activity; but still allows for butyrate-mediated apoptosis. Overexpression of p300 stimulates basal and butyrate-induced WNT signaling in some, but not all, CRC cell lines. We also evaluate the role of p300 in therapeutic approaches that target CBP. The small molecule ICG-001, in clinical trial, is a specific inhibitor of CBP-mediated WNT signaling, and previous studies have suggested that p300 is required for the activity of ICG-001. However, we report that ICG-001 maintains full activity against CBP-mediated WNT signaling in p300-deficient cell lines, including the butyrate-resistance line HCT-R. In addition, our findings evaluating combinatorial treatment of ICG-001 and butyrate in HCT-R cells may have important therapeutic implications for the treatment of butyrate-resistant CRCs.

Background The Chinese government now encourages innovation, and more specifically, crowdsourcing. Crowdsourcing, the process of shifting individual tasks to a large group, might reimagine health communication, making it more people-centred. We aimed to compare the effectiveness of a crowdsourced versus social marketing condom promotion video to promote condom use. Methods A non-inferiority randomised controlled trial was conducted in November 2015 in China. Men who have sex with men (MSM) aged 16 years or older who reported having had sexual contact without use of a condom in the preceding 3 months were recruited through a nationwide MSM website. Men were randomly allocated to one of the two arms in a 1:1 ratio using a computer algorithm and then watched one of two videos. The crowdsourced video was developed through an open contest and the social marketing video was designed by a company. Participants completed a baseline survey and follow-up surveys at 3 weeks and 3 months post-intervention. The primary outcome was incidence of sexual contact without a condom. Intention-to-treat analysis was used, with a non-inferiority margin of 10%. The trial is registered with ClinicalTrials.gov, number NCT02516930. All participants gave informed consent and the protocol was approved by Chinese (Guangdong Provincial Centre for Skin Diseases and STI Control) and American (University of North Carolina at Chapel Hill and the University of California San Francisco) institutional review boards. Findings 1173 participants were recruited to the study; 907 (77%) completed the 3-week follow up and 791 (67%) the three-month follow up. At three weeks, 146/434 (33·6%) participants in the crowdsourced group and 153/473 (32·3%) in the social marketing group reported having sexual contact without a condom. The crowdsourced intervention achieved our pre-specified non-inferiority criterion (estimated difference: +1·3% [95%CI: 4·8–7·4]). At 3 months, 196/376 (52·1%) men in the crowdsourced group and 206/415 (49·6%) in the social-marketing group reported having sexual contact without a condom (estimated difference: +2·5% [95%CI −4·5–9·5%]). The two groups reported similar HIV testing rates and other condom-related secondary outcomes. The cost of the crowdsourcing intervention was substantially lower than the social marketing intervention (16 686 vs 26 845 USD). No adverse outcomes were reported. Interpretation Crowdsourcing could be a useful tool in China, which has a large population and government support. Crowdsourcing provides a structured system for multi-sectoral input into health policy in China. Funding US National Institute of Allergy and Infectious Diseases (NIAID; 1R01AI114310); University of North Carolina (UNC)-South China Sexually Transmitted Disease Research Training Centre (Fogarty International Centre; 1D43TW009532); UNC Center for AIDS Research (NIAID; 5P30AI050410); University of California San Francisco Centre for AIDS Research (NIAID; P30 AI027763); US National Institute of Mental Health (R00MH093201 to CW); UNC Chapel Hill, Johns Hopkins University, Morehead School of Medicine and Tulane University (UJMT) Fogarty Fellowship (FIC R25TW0093); Doris Duke International Clinical Research Fellowship; US National Center for Advancing Translational Sciences (UL1TR001111).

Background Most men who have sex with men (MSM) in China do not publicly disclose their sexual orientation. This low rate of disclosure may affect sexual behaviours, testing for HIV or other sexually transmitted infections (STIs), and disease transmission. This study examined factors associated with overall sexual orientation disclosure and disclosure to a healthcare professional. Methods We did a cross-sectional online survey of MSM in China from September 23, 2014, to October 8, 2014, through three national websites. Participants completed questions covering sociodemographic information, sexual behaviors, HIV and syphilis test history, and self-reported HIV status. We defined overall disclosure as having ever disclosed sexual orientation to anyone other than a sexual partner, and healthcare professional disclosure as disclosing to a doctor or other medical provider. Eligible participants gave informed consent electronically before beginning the survey. Findings A total of 1819 men started the survey and 1424 (78%) completed it. Of 1424 participants, 62% (886/1424) reported overall disclosure, and 16% (232/1424) had disclosed to healthcare providers. In multivariate analyses, the odds of overall sexual orientation disclosure were 56% higher among MSM who used smartphone-based sex-seeking applications (adjusted OR 1·56 [95% CI 1·25–2·95]), but were lower among MSM reporting high-risk sexual risk behaviors such as sex while drunk (0·55 [0·37–0·81]) and sex while using drugs (0·66 [0·50–0·87]). The odds of disclosure to a healthcare professional were greater among MSM who had ever been tested for HIV (3·36 [2·50–4·51]) or STIs 4·92 [3·47–6·96]) or self-reported as HIV positive (1·59 [0·93–2·72]). Interpretation More than 80% of MSM surveyed had not disclosed their sexual orientation to health professionals. This low level of disclosure probably represents a major obstacle to serving the unique needs of MSM in clinical settings. Further research and action to facilitate disclosure of sexual orientation by MSM, especially to healthcare professionals, is urgently needed. Funding US National Institute of Allergy and Infectious Diseases (NIAID; 1R01AI114310); University of North Carolina (UNC)-South China STD Research Training Centre (Fogarty International Centre 1D43TW009532); UNC Center for AIDS Research (NIAID; 5P30AI050410); University of California San Francisco Centre for AIDS Research (NIAID; P30 AI027763]; US National Institute of Mental Health (R00MH093201); UNC Chapel Hill, Johns Hopkins University, Morehead School of Medicine and Tulane University (UJMT) Fogarty Fellowship (FIC R25TW0093); Doris Duke International Clinical Research Fellowship; US National Center for Advancing Translational Sciences (UL1TR001111).

Objectives of the study: We wished to (a) compare gene expression profiles between a colonic microadenoma cell line (LT97) and a metastatic colorectal cancer (CRC) cell line (SW620) in the presence and absence of butyrate, (b) determine whether the sensitivity of LT97 cells to the growth suppressive effects of butyrate correlates to a high-fold upregulation of Wnt signaling in these cells, and (c) evaluate how modulation of CBP/p300-mediated Wnt signaling influences the ability of butyrate to upregulate Wnt activity in LT97 cells. Methods: RNA was isolated from mock treated or butyrate treated LT97 microadenoma cells or SW620 metastatic CRC cells, followed by full human genome microarray analysis (Genus Biosystems). Colonic cells were transfected with Wnt reporter plasmids and treated with ICG-001 (which inhibits CBP-mediated Wnt activity) or co-transfected with a p300 expression vector or with an expression vector for KLF4, which inhibits CBP/p300 association with beta-catenin. Reporter assays, western blotting, and caspase assays were performed. Results: We demonstrate that LT97 colonic microadenoma cells differ substantially in gene expression profiles compared to a metastatic CRC cell line (SW620), both in the presence and absence of butyrate. Further, we demonstrate that the high degree of sensitivity to the growth repressive effects of butyrate of LT97 cells correlates to a marked butyrate-induced hyperactivation of Wnt activity in that cell line. Further, the induction of Wnt activity by butyrate in LT97 cells is sensitive to treatment with ICG-001, overexpression of CBP or p300, or blockade of CBP/p300-mediated Wnt activity by the transcription factor KLF4. Conclusions: Microadenoma cells, reflecting very early stage colonic neoplasia, are highly sensitive to the effects of butyrate on Wnt signaling, in a manner dependent upon CBP/p300. The findings generated from this study may lead to approaches to modulate the action of CBP/p300-mediated Wnt signaling transcriptional programs for therapeutic or chemopreventive effect. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A65. Citation Format: Darina L. Lazarova, Christopher Chiaro, Terrence Wong, Michael Bordonaro. Characterization of CBP/p300-mediated butyrate-induced Wnt activity in colonic microadenoma cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A65.

Multilevel (ML) technology increases storage capacity and data transfer rates of an optical data storage system. ML is shown to be a strong candidate for use with a high numeric aperture (NA) and blue-laser system by demonstrating good margin performance.

Background: Before 1987, the hospital survival of patients with acquired immunodeficiency syndrome, Pneumocystis carinii pneumonia, and acute respiratory failure receiving mechanical ventilation was less than 15%. Hospital survival has improved since then, but concerns have been raised that the post—hospital discharge survival of these patients remains extremely poor. This study evaluated the long-term survival of patients discharged alive after an acute episode of acute respiratory failure caused by P carinii pneumonia. Methods: A prospective cohort study was conducted for the 5-year period from May 1987 through May 1992 in an urban teaching hospital. Forty-seven patients discharged from the hospital after receiving mechanical ventilation and/or continuous positive airway pressure for acquired immunodeficiency syndrome, P carinii pneumonia, and acute respiratory failure were followed up from their initial intensive care unit admission until death or termination of the study to measure the long-term survival and cumulative probability of survival of the study cohort. Actuarial life-table analysis was performed, and long-term cumulative probability of survival was calculated on the basis of the life-table analysis. Median survival was estimated by means of the product-limit method. Results: During the 5-year follow-up of the 47 subjects, 31 patients died, 12 were unavailable for follow-up, and four were still alive at the end of the cutoff. The cumulative survival rate at 1 year was 80% (95% confidence interval, 92% to 68%); at 2 years, 49% (95% confidence interval, 65% to 34%); at 3 years, 18% (95% confidence interval, 32% to 4%); and at 4 years, 6% (95% confidence interval, 17% to 0%). Median survival time for all subjects was 602 days (1.65 years), and the longest survival time for a single patient was 1774 days (4.86 years). Conclusions: Post—hospital discharge survival of patients with acquired immunodeficiency syndrome, P carinii pneumonia, and acute respiratory failure has improved dramatically in the past decade. Patients can undergo intubation and mechanical ventilation with the hope of reasonable long-term survival. (Arch Intern Med. 1995;155:91-95)