School-based interventions for preventing HIV, sexually transmitted infections, and pregnancy in adolescents

Background School-based sexual and reproductive health programmes are widely accepted as an approach to reducing high-risk sexual behaviour among adolescents. Many studies and systematic reviews have concentrated on measuring effects on knowledge or self-reported behaviour rather than biological outcomes, such as pregnancy or prevalence of sexually transmitted infections (STIs). Objectives To evaluate the effects of school-based sexual and reproductive health programmes on sexually transmitted infections (such as HIV, herpes simplex virus, and syphilis), and pregnancy among adolescents. Search methods We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for published peer-reviewed journal articles; and ClinicalTrials.gov and the World Health Organization's (WHO) International Clinical Trials Registry Platform for prospective trials; AIDS Educaton and Global Information System (AEGIS) and National Library of Medicine (NLM) gateway for conference presentations; and the Centers for Disease Control and Prevention (CDC), UNAIDS, the WHO and the National Health Service (NHS) centre for Reviews and Dissemination (CRD) websites from 1990 to 7 April 2016. We handsearched the reference lists of all relevant papers. Selection criteria\ud We included randomized controlled trials (RCTs), both individually randomized and cluster-randomized, that evaluated school-based programmes aimed at improving the sexual and reproductive health of adolescents. Data collection and analysis Two review authors independently assessed trials for inclusion, evaluated risk of bias, and extracted data. When appropriate, we obtained summary measures of treatment effect through a random-effects meta-analysis and we reported them using risk ratios (RR) with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach. Main results We included eight cluster-RCTs that enrolled 55,157 participants. Five trials were conducted in sub-Saharan Africa (Malawi, South Africa, Tanzania, Zimbabwe, and Kenya), one in Latin America (Chile), and two in Europe (England and Scotland). Sexual and reproductive health educational programmes Six trials evaluated school-based educational interventions. In these trials, the educational programmes evaluated had no demonstrable effect on the prevalence of HIV (RR 1.03, 95% CI 0.80 to 1.32, three trials; 14,163 participants; low certainty evidence), or other STIs (herpes simplex virus prevalence: RR 1.04, 95% CI 0.94 to 1.15; three trials, 17,445 participants; moderate certainty evidence; syphilis prevalence: RR 0.81, 95% CI 0.47 to 1.39; one trial, 6977 participants; low certainty evidence). There was also no apparent effect on the number of young women who were pregnant at the end of the trial (RR 0.99, 95% CI 0.84 to 1.16; three trials, 8280 participants; moderate certainty evidence). Material or monetary incentive-based programmes to promote school attendance Two trials evaluated incentive-based programmes to promote school attendance. In these two trials, the incentives used had no demonstrable effect on HIV prevalence (RR 1.23, 95% CI 0.51 to 2.96; two trials, 3805 participants; low certainty evidence). Compared to controls, the prevalence of herpes simplex virus infection was lower in young women receiving a monthly cash incentive to stay in school (RR 0.30, 95% CI 0.11 to 0.85), but not in young people given free school uniforms (Data not pooled, two trials, 7229 participants; very low certainty evidence). One trial evaluated the effects on syphilis and the prevalence was too low to detect or exclude effects confidently (RR 0.41, 95% CI 0.05 to 3.27; one trial, 1291 participants; very low certainty evidence). However, the number of young women who were pregnant at the end of the trial was lower among those who received incentives (RR 0.76, 95% CI 0.58 to 0.99; two trials, 4200 participants; low certainty evidence). Combined educational and incentive-based programmes The single trial that evaluated free school uniforms also included a trial arm in which participants received both uniforms and a programme of sexual and reproductive education. In this trial arm herpes simplex virus infection was reduced (RR 0.82, 95% CI 0.68 to 0.99; one trial, 5899 participants; low certainty evidence), predominantly in young women, but no effect was detected for HIV or pregnancy (low certainty evidence). Authors' conclusions There is a continued need to provide health services to adolescents that include contraceptive choices and condoms and that involve them in the design of services. Schools may be a good place in which to provide these services. There is little evidence that educational curriculum-based programmes alone are effective in improving sexual and reproductive health outcomes for adolescents. Incentive-based interventions that focus on keeping young people in secondary school may reduce adolescent pregnancy but further trials are needed to confirm this

Eye Controlled Electric Wheel Chair

ABSTRACT: This paper delivers a method to guide and control the wheelchair for disabled people based on movement of eye. This concept can be used for people with loco-motor disabilities. The proposed system involves three stages: image detection, image processing and sending of control signals wheelchair. The eye movement is detected using a head mounted camera. The images of the eye will be sent to the laptop where the images will be processed using Python software. The corresponding output signals are then send to the motor driving circuit which control the motors

Noise reduction in ultra-low light digital holographic microscopy using neural networks

Live cell imaging is challenging because the difficult balance of maintaining both cell viability and high signal to noise ratio throughout the entire imaging duration. Label free quantitative light microscopy techniques are powerful tools to image the volumetric activities in living cellular and sub-cellular biological systems, however there are minimal ways to identify phototoxicity. In this paper, we investigate the use of neural network to restore quantitative digital hologram micrographs at ultra-low light levels down to 0.06 /2 which approximately two orders of magnitude lower than sunlight. By developing an adaptive image restoration method specifically tailored for digital holograms, we demonstrated the 2x improvement in SSIM over existing denoising methods. This demonstration could open up new avenues for high resolution holographic microscopy using deep ultraviolet coherent sources and achieve high-resolution imaging with ultralow light illuminatio

Holo-UNet: hologram-to-hologram neural network restoration for high fidelity low light quantitative phase imaging of live cells

Intensity shot noise in digital holograms distorts the quality of the phase images after phase retrieval, limiting the usefulness of quantitative phase microscopy (QPM) systems in long term live cell imaging. In this paper, we devise a hologram-to-hologram neural network, Holo-UNet, that restores high quality digital holograms under high shot noise conditions (sub-mW/cm2 intensities) at high acquisition rates (sub-milliseconds). In comparison to current phase recovery methods, Holo-UNet denoises the recorded hologram, and so prevents shot noise from propagating through the phase retrieval step that in turn adversely affects phase and intensity images. Holo-UNet was tested on 2 independent QPM systems without any adjustment to the hardware setting. In both cases, Holo-UNet outperformed existing phase recovery and block-matching techniques by ∼ 1.8 folds in phase fidelity as measured by SSIM. Holo-UNet is immediately applicable to a wide range of other high-speed interferometric phase imaging techniques. The network paves the way towards the expansion of high-speed low light QPM biological imaging with minimal dependence on hardware constraints.Australian Research Council (DE160100843, DP190100039, DP200100364

A global sampling approach to designing and reengineering RNA secondary structures

The development of algorithms for designing artificial RNA sequences that fold into specific secondary structures has many potential biomedical and synthetic biology applications. To date, this problem remains computationally difficult, and current strategies to address it resort to heuristics and stochastic search techniques. The most popular methods consist of two steps: First a random seed sequence is generated; next, this seed is progressively modified (i.e. mutated) to adopt the desired folding properties. Although computationally inexpensive, this approach raises several questions such as (i) the influence of the seed; and (ii) the efficiency of single-path directed searches that may be affected by energy barriers in the mutational landscape. In this article, we present RNA-ensign, a novel paradigm for RNA design. Instead of taking a progressive adaptive walk driven by local search criteria, we use an efficient global sampling algorithm to examine large regions of the mutational landscape under structural and thermodynamical constraints until a solution is found. When considering the influence of the seeds and the target secondary structures, our results show that, compared to single-path directed searches, our approach is more robust, succeeds more often and generates more thermodynamically stable sequences. An ensemble approach to RNA design is thus well worth pursuing as a complement to existing approaches. RNA-ensign is available at http://csb.cs.mcgill.ca/RNAensign.National Science Foundation (U.S.). Graduate Research Fellowship ProgramNatural Sciences and Engineering Research Council of Canada (NSERC) (RGPIN ) (386596-10)Fonds québécois de la recherche sur la nature et les technologies (PR-146375)National Institutes of Health (U.S.) (Grant GM081871)Natural Sciences and Engineering Research Council of Canada (NSERC)National Institutes of Health (U.S.

Metabolic adaptation drives arsenic trioxide resistance in acute promyelocytic leukemia.

Acquired genetic mutations can confer resistance to arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL). However, such resistance-conferring mutations are rare and do not explain most disease recurrence seen in the clinic. We have generated stable ATO-resistant promyelocytic cell lines that are also less sensitive to ATRA and the combination of ATO and ATRA compared to the sensitive cell line. Characterization of these in-house generated resistant cell lines showed significant differences in immunophenotype, drug transporter expression, anti-apoptotic protein dependence, and PML-RARA mutation. Gene expression profiling revealed prominent dysregulation of the cellular metabolic pathways in these ATO resistant APL cell lines. Glycolytic inhibition by 2-DG was sufficient and comparable to the standard of care (ATO) in targeting the sensitive APL cell line. 2-DG was also effective in the in vivo transplantable APL mouse model; however, it did not affect the ATO resistant cell lines. In contrast, the resistant cell lines were significantly affected by compounds targeting the mitochondrial respiration when combined with ATO, irrespective of the ATO resistance-conferring genetic mutations or the pattern of their anti-apoptotic protein dependency. Our data demonstrate that the addition of mitocans in combination with ATO can overcome ATO resistance. We further show that this combination has the potential in the treatment of non-M3 AML and relapsed APL. The translation of this approach in the clinic needs to be explored further

Optimization of the doxycycline-dependent simian immunodeficiency virus through in vitro evolution

<p>Abstract</p> <p>Background</p> <p>Vaccination of macaques with live attenuated simian immunodeficiency virus (SIV) provides significant protection against the wild-type virus. The use of a live attenuated human immunodeficiency virus (HIV) as AIDS vaccine in humans is however considered unsafe because of the risk that the attenuated virus may accumulate genetic changes during persistence and evolve to a pathogenic variant. We earlier presented a conditionally live HIV-1 variant that replicates exclusively in the presence of doxycycline (dox). Replication of this vaccine strain can be limited to the time that is needed to provide full protection through transient dox administration. Since the effectiveness and safety of such a conditionally live virus vaccine should be tested in macaques, we constructed a similar dox-dependent SIV variant. The Tat-TAR transcription control mechanism in this virus was inactivated through mutation and functionally replaced by the dox-inducible Tet-On regulatory system. This SIV-rtTA variant replicated in a dox-dependent manner in T cell lines, but not as efficiently as the parental SIVmac239 strain. Since macaque studies will likely require an efficiently replicating variant, we set out to optimize SIV-rtTA through in vitro viral evolution.</p> <p>Results</p> <p>Upon long-term culturing of SIV-rtTA, additional nucleotide substitutions were observed in TAR that affect the structure of this RNA element but that do not restore Tat binding. We demonstrate that the bulge and loop mutations that we had introduced in the TAR element of SIV-rtTA to inactivate the Tat-TAR mechanism, shifted the equilibrium between two alternative conformations of TAR. The additional TAR mutations observed in the evolved variants partially or completely restored this equilibrium, which suggests that the balance between the two TAR conformations is important for efficient viral replication. Moreover, SIV-rtTA acquired mutations in the U3 promoter region. We demonstrate that these TAR and U3 changes improve viral replication in T-cell lines and macaque peripheral blood mononuclear cells (PBMC) but do not affect dox-control.</p> <p>Conclusion</p> <p>The dox-dependent SIV-rtTA variant was optimized by viral evolution, yielding variants that can be used to test the conditionally live virus vaccine approach and as a tool in SIV biology studies and vaccine research.</p