Right ventricular dysfunction after resuscitation predicts poor outcomes in cardiac arrest patients independent of left ventricular function.

OBJECTIVE: Determination of clinical outcomes following resuscitation from cardiac arrest remains elusive in the immediate post-arrest period. Echocardiographic assessment shortly after resuscitation has largely focused on left ventricular (LV) function. We aimed to determine whether post-arrest right ventricular (RV) dysfunction predicts worse survival and poor neurologic outcome in cardiac arrest patients, independent of LV dysfunction. METHODS: A single-center, retrospective cohort study at a tertiary care university hospital participating in the Penn Alliance for Therapeutic Hypothermia (PATH) Registry between 2000 and 2012. PATIENTS: 291 in- and out-of-hospital adult cardiac arrest patients at the University of Pennsylvania who had return of spontaneous circulation (ROSC) and post-arrest echocardiograms. MEASUREMENTS AND MAIN RESULTS: Of the 291 patients, 57% were male, with a mean age of 59 ± 16 years. 179 (63%) patients had LV dysfunction, 173 (59%) had RV dysfunction, and 124 (44%) had biventricular dysfunction on the initial post-arrest echocardiogram. Independent of LV function, RV dysfunction was predictive of worse survival (mild or moderate: OR 0.51, CI 0.26-0.99, p CONCLUSIONS: Echocardiographic findings of post-arrest RV dysfunction were equally prevalent as LV dysfunction. RV dysfunction was significantly predictive of worse outcomes in post-arrest patients after accounting for LV dysfunction. Post-arrest RV dysfunction may be useful for risk stratification and management in this high-mortality population

Water dispersible microbicidal cellulose acetate phthalate film

BACKGROUND: Cellulose acetate phthalate (CAP) has been used for several decades in the pharmaceutical industry for enteric film coating of oral tablets and capsules. Micronized CAP, available commercially as "Aquateric" and containing additional ingredients required for micronization, used for tablet coating from water dispersions, was shown to adsorb and inactivate the human immunodeficiency virus (HIV-1), herpesviruses (HSV) and other sexually transmitted disease (STD) pathogens. Earlier studies indicate that a gel formulation of micronized CAP has a potential as a topical microbicide for prevention of STDs including the acquired immunodeficiency syndrome (AIDS). The objective of endeavors described here was to develop a water dispersible CAP film amenable to inexpensive industrial mass production. METHODS: CAP and hydroxypropyl cellulose (HPC) were dissolved in different organic solvent mixtures, poured into dishes, and the solvents evaporated. Graded quantities of a resulting selected film were mixed for 5 min at 37°C with HIV-1, HSV and other STD pathogens, respectively. Residual infectivity of the treated viruses and bacteria was determined. RESULTS: The prerequisites for producing CAP films which are soft, flexible and dispersible in water, resulting in smooth gels, are combining CAP with HPC (other cellulose derivatives are unsuitable), and casting from organic solvent mixtures containing ≈50 to ≈65% ethanol (EtOH). The films are ≈100 µ thick and have a textured surface with alternating protrusions and depressions revealed by scanning electron microscopy. The films, before complete conversion into a gel, rapidly inactivated HIV-1 and HSV and reduced the infectivity of non-viral STD pathogens >1,000-fold. CONCLUSIONS: Soft pliable CAP-HPC composite films can be generated by casting from organic solvent mixtures containing EtOH. The films rapidly reduce the infectivity of several STD pathogens, including HIV-1. They are converted into gels and thus do not have to be removed following application and use. In addition to their potential as topical microbicides, the films have promise for mucosal delivery of pharmaceuticals other than CAP

An assessment of vulnerability to HIV infection of boatmen in Teknaf, Bangladesh

<p>Abstract</p> <p>Background</p> <p>Mobile population groups are at high risk for contracting HIV infection. Many factors contribute to this risk including high prevalence of risky behavior and increased risk of violence due to conflict and war. The Naf River serves as the primary border crossing point between Teknaf, Bangladesh and Mynamar [Burma] for both official and unofficial travel of people and goods. Little is known about the risk behavior of boatmen who travel back and forth between Teknaf and Myanmar. However, we hypothesize that boatmen may act as a bridging population for HIV/AIDS between the high-prevalence country of Myanmar and the low-prevalence country of Bangladesh.</p> <p>Methods</p> <p>Methods included initial rapport building with community members, mapping of boatmen communities, and in-depth qualitative interviews with key informants and members from other vulnerable groups such as spouses of boatmen, commercial female sex workers, and injecting drug users. Information from the first three stages was used to create a cross-sectional survey that was administered to 433 boatmen.</p> <p>Results</p> <p>Over 40% of the boatmen had visited Myanmar during the course of their work. 17% of these boatmen had sex with CSW while abroad. There was a significant correlation found between the number of nights spent in Myanmar and sex with commercial sex workers.</p> <p>In the past year, 19% of all boatmen surveyed had sex with another man. 14% of boatmen had participated in group sex, with groups ranging in size from three to fourteen people. Condom use was rare {0 to 4.7% during the last month}, irrespective of types of sex partners. Regression analysis showed that boatmen who were 25 years and older were statistically less likely to have sexual intercourse with non- marital female partners in the last year compared to the boatmen aged less than 25 years. Similarly deep-sea fishing boatmen and non-fishing boatmen were statistically less likely to have sexual intercourse with non- marital female partners in the last year compared to the day long fishing boatmen adjusting for all other variables. Boatmen's knowledge regarding HIV transmission and personal risk perception for contracting HIV was low.</p> <p>Conclusion</p> <p>Boatmen in Teknaf are an integral part of a high-risk sexual behaviour network between Myanmar and Bangladesh. They are at risk of obtaining HIV infection due to cross border mobility and unsafe sexual practices. There is an urgent need for designing interventions targeting boatmen in Teknaf to combat an impending epidemic of HIV among this group. They could be included in the serological surveillance as a vulnerable group. Interventions need to address issues on both sides of the border, other vulnerable groups, and refugees. Strong political will and cross border collaboration is mandatory for such interventions.</p

Multi-timescale analysis of a metabolic network in synthetic biology: a kinetic model for 3-hydroxypropionic acid production via beta-alanine

A biosustainable production route for 3-hydroxypropionic acid (3HP), an important platform chemical, would allow 3HP to be produced without using fossil fuels. We are interested in investigating a potential biochemical route to 3HP from pyruvate through b -alanine and, in this paper, we develop and solve a mathematical model for the reaction kinetics of the metabolites involved in this pathway. We consider two limiting cases, one where the levels of pyruvate are never replenished, the other where the levels of pyruvate are continuously replenished and thus kept constant. We exploit the natural separation of both the time scales and the metabolite concentrations to make significant asymptotic progress in understanding the system without resorting to computationally expensive parameter sweeps. Using our asymptotic results, we are able to predict the most important reactions to maximize the production of 3HP in this system while reducing the maximum amount of the toxic intermediate compound malonic semialdehyde present at any one time, and thus we are able to recommend which enzymes experimentalists should focus on manipulating

Interim data monitoring to enroll higher-risk participants in HIV prevention trials

<p>Abstract</p> <p>Background</p> <p>Lower-than-expected incidence of HIV undermines sample size calculations and compromises the power of a HIV prevention trial. We evaluated the effectiveness of interim monitoring of HIV infection rates and on-going modification of recruitment strategies to enroll women at higher risk of HIV in the Cellulose Sulfate Phase III study in Nigeria.</p> <p>Methods</p> <p>We analyzed prevalence and incidence of HIV and other sexually transmitted infections, demographic and sexual behavior characteristics aggregated over the treatment groups on a quarterly basis. The site investigators were advised on their recruitment strategies based on the findings of the interim analyses.</p> <p>Results</p> <p>A total of 3619 women were screened and 1644 enrolled at the Ikeja and Apapa clinics in Lagos, and at the Central and Peripheral clinics in Port Harcourt. Twelve months after study initiation, the overall incidence of HIV was less than one-third of the pre-study assumption, with rates of HIV that varied substantially between clinics. Due to the low prevalence and incidence rates of HIV, it was decided to close the Ikeja clinic in Lagos and to find new catchment areas in Port Harcourt. This strategy was associated with an almost two-fold increase in observed HIV incidence during the second year of the study.</p> <p>Conclusion</p> <p>Given the difficulties in estimating HIV incidence, a close monitoring of HIV prevalence and incidence rates during a trial is warranted. The on-going modification of recruitment strategies based on the regular analysis of HIV rates appeared to be an efficient method for targeting populations at greatest risk of HIV infection and increasing study power in the Nigeria trial.</p> <p>Trial Registration</p> <p>The trial was registered with the ClinicalTrials.gov registry under #NCT00120770 <url>http://clinicaltrials.gov/ct2/show/NCT00120770</url></p

Pregnancy Incidence and Correlates during the HVTN 503 Phambili HIV Vaccine Trial Conducted among South African Women

HIV prevention trials are increasingly being conducted in sub-Saharan Africa. Women at risk for HIV are also at risk of pregnancy. To maximize safety, women agree to avoid pregnancy during trials, yet pregnancies occur. Using data from the HVTN 503/"Phambili" vaccine trial, we report pregnancy incidence during and after the vaccination period and identify factors, measured at screening, associated with incident pregnancy.To enrol in the trial, women agreed and were supported to avoid pregnancy until 1 month after their third and final vaccination ("vaccination period"), corresponding to the first 7 months of follow-up. Unsterilized women, pooled across study arms, were analyzed. Poisson regression compared pregnancy rates during and after the vaccination period. Cox proportional hazards regression identified associations with first pregnancy.Among 352 women (median age 23 yrs; median follow-up 1.5 yrs), pregnancy incidence was 9.6/100 women-years overall and 6.8/100 w-yrs and 11.3/100 w-yrs during and after the vaccination period, respectively [Rate Ratio = 0.60 (0.32-1.14), p = 0.10]. In multivariable analysis, pregnancy was reduced among women who: enrolled at sites providing contraception on-site [HR = 0.43, 95% CI (0.22-0.86)]; entered the trial as injectable contraceptive users [HR = 0.37 (0.21-0.67)] or as consistent condom users (trend) [HR = 0.54 (0.28-1.04)]. Compared with women with a single partner of HIV-unknown status, pregnancy rates were increased among women with: a single partner whose status was HIV-negative [HR = 2.34(1.16-4.73)] and; 2 partners both of HIV-unknown status [HR = 4.42(1.59-12.29)]. Women with 2 more of these risk factors: marijuana use, heavy drinking, or use of either during sex, had increased pregnancy incidence [HR = 2.66 (1.24-5.72)].It is possible to screen South African women for pregnancy risk at trial entry. Providing injectable contraception for free on-site and supporting consistent condom use may reduce incident pregnancy. Screening should determine the substance use, partnering, and HIV status of both members of the couple for both pregnancy and HIV prevention.SA National Health Research Database DOH-27-0207-1539; Clinicaltrials.gov NCT00413725

Are Women Who Work in Bars, Guesthouses and Similar Facilities a Suitable Study Population for Vaginal Microbicide Trials in Africa?

BACKGROUND: A feasibility study was conducted to investigate whether an occupational at-risk cohort of women in Mwanza, Tanzania are a suitable study population for future phase III vaginal microbicide trials. METHODOLOGY/PRINCIPAL FINDINGS: 1573 women aged 16-54 y working in traditional and modern bars, restaurants, hotels, guesthouses or as local food-handlers were enrolled at community-based reproductive health clinics, provided specimens for HIV/STI and pregnancy testing, and asked to attend three-monthly clinical follow-up visits for 12-months. HIV positive and negative women were eligible to enter the feasibility study and to receive free reproductive health services at any time. HIV prevalence at baseline was 26.5% (417/1573). HIV incidence among 1156 sero-negative women attending at baseline was 2.9/100PYs. Among 1020 HIV sero-negative, non-pregnant women, HIV incidence was 2.0/100PYs, HSV-2 incidence 12.7/100PYs and pregnancy rate 17.8/100PYs. Retention at three-months was 76.3% (778/1020). Among 771 HIV sero-negative, non-pregnant women attending at three-months, subsequent follow-up at 6, 9 and 12-months was 83.7%, 79.6%, and 72.1% respectively. Older women, those who had not moved home or changed their place of work in the last year, and women working in traditional bars or as local food handlers had the highest re-attendance. CONCLUSIONS/SIGNIFICANCE: Women working in food outlets and recreational facilities in Tanzania and other parts of Africa may be a suitable study population for microbicide and other HIV prevention trials. Effective locally-appropriate strategies to address high pregnancy rates and early losses to follow-up are essential to minimise risk to clinical trials in these settings

Robustness of optimal channel reservation using handover prediction in multiservice wireless networks

The aim of our study is to obtain theoretical limits for the gain that can be expected when using handover prediction and to determine the sensitivity of the system performance against different parameters. We apply an average-reward reinforcement learning approach based on afterstates to the design of optimal admission control policies in mobile multimedia cellular networks where predictive information related to the occurrence of future handovers is available. We consider a type of predictor that labels active mobile terminals in the cell neighborhood a fixed amount of time before handovers are predicted to occur, which we call the anticipation time. The admission controller exploits this information to reserve resources efficiently. We show that there exists an optimum value for the anticipation time at which the highest performance gain is obtained. Although the optimum anticipation time depends on system parameters, we find that its value changes very little when the system parameters vary within a reasonable range. We also find that, in terms of system performance, deploying prediction is always advantageous when compared to a system without prediction, even when the system parameters are estimated with poor precision. © Springer Science+Business Media, LLC 2012.The authors would like to thank the reviewers for their valuable comments that helped to improve the quality of the paper. This work has been supported by the Spanish Ministry of Education and Science and European Comission (30% PGE, 70% FEDER) under projects TIN2008-06739-C04-02 and TIN2010-21378-C02-02 and by Comunidad de Madrid through project S-2009/TIC-1468.Martínez Bauset, J.; Giménez Guzmán, JM.; Pla, V. (2012). Robustness of optimal channel reservation using handover prediction in multiservice wireless networks. Wireless Networks. 18(6):621-633. https://doi.org/10.1007/s11276-012-0423-6S621633186Ji, S., Chen, W., Ding, X., Chen, Y., Zhao, C., & Hu, C. (2010). Potential benefits of GPS/GLONASS/GALILEO integration in an urban canyon–Hong Kong. Journal of Navigation, 63(4), 681–693.Soh, W., & Kim, H. (2006). A predictive bandwidth reservation scheme using mobile positioning and road topology information. IEEE/ACM Transactions on Networking, 14(5), 1078–1091.Kwon, H., Yang, M., Park, A., & Venkatesan, S. (2008). Handover prediction strategy for 3G-WLAN overlay networks. In Proceedings: IEEE network operations and management symposium (NOMS) (pp. 819–822).Huang, C., Shen, H., & Chuang, Y. (2010). An adaptive bandwidth reservation scheme for 4G cellular networks using flexible 2-tier cell structure. Expert Systems with Applications, 37(9), 6414–6420.Wanalertlak, W., Lee, B., Yu, C., Kim, M., Park, S., & Kim, W. (2011). Behavior-based mobility prediction for seamless handoffs in mobile wireless networks. Wireless Networks, 17(3), 645–658.Becvar, Z., Mach, P., & Simak, B. (2011). Improvement of handover prediction in mobile WiMAX by using two thresholds. Computer Networks, 55, 3759–3773.Sgora, A., & Vergados, D. (2009). Handoff prioritization and decision schemes in wireless cellular networks: a survey. IEEE Communications Surveys and Tutorials, 11(4), 57–77.Choi, S., & Shin, K. G. (2002). Adaptive bandwidth reservation and admission control in QoS-sensitive cellular networks. IEEE Transactions on Parallel and Distributed Systems, 13(9), 882–897.Ye, Z., Law, L., Krishnamurthy, S., Xu, Z., Dhirakaosal, S., Tripathi, S., & Molle, M. (2007). Predictive channel reservation for handoff prioritization in wireless cellular networks. Computer Networks, 51(3), 798–822.Abdulova, V., & Aybay, I. (2011). Predictive mobile-oriented channel reservation schemes in wireless cellular networks. Wireless Networks, 17(1), 149–166.Ramjee, R., Nagarajan, R., & Towsley, D. (1997). On optimal call admission control in cellular networks. Wireless Networks, 3(1), 29–41.Bartolini, N. (2001). Handoff and optimal channel assignment in wireless networks. Mobile Networks and Applications, 6(6), 511–524.Bartolini, N., & Chlamtac, I. (2002). Call admission control in wireless multimedia networks. In Proceedings: Personal, indoor and mobile radio communications (PIMRC) (pp. 285–289).Pla, V., & Casares-Giner, V. (2003). Optimal admission control policies in multiservice cellular networks. In Proceedings of the international network optimization conference (INOC) (pp. 466–471).Chu, K., Hung, L., & Lin, F. (2009). Adaptive channel reservation for call admission control to support prioritized soft handoff calls in a cellular CDMA system. Annals of Telecommunications, 64(11), 777–791.El-Alfy, E., & Yao, Y. (2011). Comparing a class of dynamic model-based reinforcement learning schemes for handoff prioritization in mobile communication networks. Expert Systems With Applications, 38(7), 8730–8737.Gimenez-Guzman, J. M., Martinez-Bauset, J., & Pla, V. (2007). A reinforcement learning approach for admission control in mobile multimedia networks with predictive information. IEICE Transactions on Communications , E-90B(7), 1663–1673.Sutton R., Barto A. G. (1998) Reinforcement learning: An introduction. The MIT press, Cambridge, MassachusettsBusoniu, L., Babuska, R., De Schutter, B., & Ernst, D. (2010). Reinforcement learning and dynamic programming using function approximators. Boca Raton, FL: CRC Press.Watkins, C., & Dayan, P. (1992). Q-learning. Machine learning, 8(3–4), 279–292.Brown, T. (2001). Switch packet arbitration via queue-learning. Advances in Neural Information Processing Systems, 14, 1337–1344.Proper, S., & Tadepalli, P. (2006). Scaling model-based average-reward reinforcement learning for product delivery. In Proceedings 17th European conference on machine learning (pp. 735–742).Driessens, K., Ramon, J., & Gärtner, T. (2006). Graph kernels and Gaussian processes for relational reinforcement learning. Machine Learning, 64(1), 91–119.Banerjee, B., & Stone, P. (2007). General game learning using knowledge transfer. In Proceedings 20th international joint conference on artificial intelligence (pp. 672–677).Martinez-Bauset, J., Pla, V., Garcia-Roger, D., Domenech-Benlloch, M. J., & Gimenez-Guzman, J. M. (2008). Designing admission control policies to minimize blocking/forced-termination. In G. Ming, Y. Pan & P. Fan (Eds.), Advances in wireless networks: Performance modelling, analysis and enhancement (pp. 359–390). New York: Nova Science Pub Inc.Biswas, S., & Sengupta, B. (1997). Call admissibility for multirate traffic in wireless ATM networks. In Proceedings IEEE INFOCOM (2, pp. 649–657).Evans, J. S., & Everitt, D. (1999). Effective bandwidth-based admission control for multiservice CDMA cellular networks. IEEE Transactions on Vehicular Technology, 48(1), 36–46.Gilhousen, K., Jacobs, I., Padovani, R., Viterbi, A., Weaver, L. A. J., & Wheatley, C. E., III. (1991). On the capacity of a cellular CDMA system. IEEE Transactions on Vehicular Technology, 40(2), 303–312.Hegde, N., & Altman, E. (2006). Capacity of multiservice WCDMA networks with variable GoS. Wireless Networks, 12, 241–253.Ben-Shimol, Y., Kitroser, I., & Dinitz, Y. (2006). Two-dimensional mapping for wireless OFDMA systems. IEEE Transactions on Broadcasting, 52(3), 388–396.Gao, D., Cai, J., & Ngan, K. N. (2005). Admission control in IEEE 802.11e wireless LANs. IEEE Network, 19(4), 6–13.Liu, T., Bahl, P., & Chlamtac, I. (1998). Mobility modeling, location tracking, and trajectory prediction in wireless ATM networks. IEEE Journal on Selected Areas in Communications, 16(6), 922–936.Hu, F., & Sharma, N. (2004). Priority-determined multiclass handoff scheme with guaranteed mobile qos in wireless multimedia networks. IEEE Transactions on Vehicular Technology, 53(1), 118–135.Chan, J., & Seneviratne, A. (1999). A practical user mobility prediction algorithm for supporting adaptive QoS in wireless networks. In Proceedings IEEE international conference on networks (ICON) (pp. 104–111).Jayasuriya, A., & Asenstorfer, J. (2002). Mobility prediction model for cellular networks based on the observed traffic patterns. In Proceedings of IASTED international conference on wireless and optical communication (WOC) (pp. 386–391).Diederich, J., & Zitterbart, M. (2005). A simple and scalable handoff prioritization scheme. Computer Communications, 28(7), 773–789.Rashad, S., Kantardzic, M., & Kumar, A. (2006). User mobility oriented predictive call admission control and resource reservation for next-generation mobile networks. Journal of Parallel and Distributed Computing, 66(7), 971–988.Soh, W. -S., & Kim, H. (2003). QoS provisioning in cellular networks based on mobility prediction techniques. IEEE Communications Magazine, 41(1), 86 – 92.Lott, M., Siebert, M., Bonjour, S., vonHugo, D., & Weckerle, M. (2004). Interworking of WLAN and 3G systems. Proceedings IEE Communications, 151(5), 507 – 513.Sanabani, M., Shamala, S., Othman, M., & Zukarnain, Z. (2007). An enhanced bandwidth reservation scheme based on road topology information for QoS sensitive multimedia wireless cellular networks. In Proceedings of the 2007 international conference on computational science and its applications—Part II (ICCSA) (pp. 261–274).Mahadevan, S. (1996). Average reward reinforcement learning: Foundations, algorithms, and empirical results. Machine Learning, 22(1–3), 159–196.Puterman, M. L. (1994). Markov decision processes: Discrete stochastic dynamic programming. New York: Wiley.Das, T. K., Gosavi, A., Mahadevan, S., & Marchalleck, N. (1999). Solving semi-markov decision problems using average reward reinforcement learning. Management Science, 45(4), 560–574.Darken, C., Chang, J., & Moody, J. (1992). Learning rate schedules for faster stochastic gradient search. In Proceedings of the IEEE-SP workshop on neural networks for signal processing II. (pp. 3–12)