Comparing effects of tobacco use prevention modalities: need for complex system models

Many modalities of tobacco use prevention programming have been implemented including various policy regulations (tax increases, warning labels, limits on access, smoke-free policies, and restrictions on marketing), mass media programming, school-based classroom education, family involvement, and involvement of community agents (i.e., medical, social, political). The present manuscript provides a glance at these modalities to compare relative and combined impact of them on youth tobacco use. In a majority of trials, community-wide programming, which includes multiple modalities, has not been found to achieve impacts greater than single modality programming. Possibly, the most effective means of prevention involves a careful selection of program type combinations. Also, it is likely that a mechanism for coordinating maximally across program types (e.g., staging of programming) is needed to encourage a synergistic impact. Studying tobacco use prevention as a complex system is considered as a means to maximize effects from combinations of prevention types. Future studies will need to more systematically consider the role of combined programming

Organizational network strengthening effects on antiretroviral therapy initiation and adherence

The WHO recommends antiretroviral therapy (ART) initiation immediately after HIV diagnosis. When HIV services are fragmented and poorly coordinated, initiation of ART can be delayed. MEASURE Evaluation conducted an organizational network intervention in Addis Ababa, Ethiopia, which increased referral network density and client satisfaction in the intervention versus control networks. The objective of our study was to extend the parent study by assessing effects of network density on the speed of ART initiation and adherence to ART. Measures of client-time since HIV diagnosis, use of ART, satisfaction with HIV-related services, and adherence were obtained from cross-sectional interviews with female service recipients with HIV/AIDS at baseline (T1, 402) and at 18-month follow-up (T2, 524) and compared between network sites. We used weighted least squares estimation with probit regression techniques in a structural equation modeling framework for analyses. On average at follow-up, clients in the intervention network were more likely to have quicker ART initiation, and were initiated on ART 15 days faster than clients in the control network. Moreover, quicker ART initiation was associated with higher adherence. A unit increase in speed of ART initiation was associated with 0.5 points increase in latent adherence score in the intervention group (ρ < .05). Satisfaction with care positively predicted adherence to ART. Network density had no direct effect on ART adherence. This quasi-experiment demonstrated that increased referral network density, through improved HIV client referrals, can enhance speed of ART initiation, resulting in improved adherence. © Society of Behavioral Medicine 2018

Integrating complex systems science into road safety research and practice, Part 2: Applying systems tools to the problem of increasing pedestrian death rates

Objectives To provide a specific example of how systems dynamics tools can increase understanding of stakeholder mental models' and generate robust systems-based hypotheses about the escalating problem of rising pedestrian death rates in the USA. Methods We designed and facilitated two group model building (GMB) workshops. Participants generated causal loop diagrams (CLDs) individually and in small groups to explore hypotheses concerning time-dynamic interacting factors underlying the increasing rates of pedestrian deaths. Using a grounded theory approach, research team members synthesised the structures and hypotheses into a single CLD. Results CLDs from the 41 participants indicated four core factors hypothesised to have a direct impact on pedestrian fatalities: pedestrian-vehicle crashes, vehicle speed at the time of the crash, vehicle size/dimensions and emergency response time. Participants diagrammed how actions and reactions impacted these proximal factors over time and led to ripple effects throughout a larger system to generate an increase in pedestrian deaths. Hypothesised contributing mechanisms fell within the following broad categories: community responses; research, policy and industry influence; potential unintended consequences of responses to pedestrian deaths; and the role of sprawl. Conclusions This application of systems science tools suggested several strategies for advancing injury prevention research and practice. The project generated robust hypotheses and advanced stakeholder communication and depth of understanding and engagement in this key issue. The CLD and GMB process detailed in this study provides a concrete example of how systems tools can be adopted and applied to a transportation safety topic

Evidence for the decay B0->eta pi^0

We report a search for the charmless hadronic decay $B^0\to\eta \pi^0$ with a data sample corresponding to an integrated luminosity of 694 $\rm fb^{-1}$ containing $753\times10^6$ $B\bar{B}$ pairs. The data were collected by the Belle experiment running on the $\Upsilon(4S)$ resonance at the KEKB $e^+e^-$ collider. We measure a branching fraction $\mathcal{B}(B^0\to\eta\pi^0)=(4.1^{+1.7+0.5}_{-1.5-0.7})\times 10^{-7}$, where the first uncertainty is statistical and the second is systematic. Our measurement gives an upper limit of $\mathcal{B}(B^0\to\eta\pi^0)<6.5\times 10^{-7}$ at 90\% confidence level. The signal has a significance of $3.0$ standard deviations and constitutes the first evidence for this decay mode.Comment: 11 pages, 3 figures, 2 tables, submitted to Physical Review D(R

Semaphorin 6D regulates the late phase of CD4+ T cell primary immune responses

The semaphorin and plexin family of ligand and receptor proteins provides important axon guidance cues required for development. Recent studies have expanded the role of semaphorins and plexins in the regulation of cardiac, circulatory and immune system function. Within the immune system, semaphorins and plexins regulate cell–cell interactions through a complex network of receptor and ligand pairs. Immune cells at different stages of development often express multiple semaphorins and plexins, leading to multivariate interactions, involving more than one ligand and receptor within each functional group. Because of this complexity, the significance of semaphorin and plexin regulation on individual immune cell types has yet to be fully appreciated. In this work, we examined the regulation of T cells by semaphorin 6D. Both in vitro and in vivo T cell stimulation enhanced semaphorin 6D expression. However, semaphorin 6D was only expressed by a majority of T cells during the late phases of activation. Consequently, the targeted disruption of semaphorin 6D receptor–ligand interactions inhibited T cell proliferation at late but not early phases of activation. This proliferation defect was associated with reduced linker of activated T cells protein phosphorylation, which may reflect semaphorin 6D regulation of c-Abl kinase activity. Semaphorin 6D disruption also inhibited expression of CD127, which is required during the multiphase antigen-presenting cell and T cell interactions leading to selection of long-lived lymphocytes. This work reveals a role for semaphorin 6D as a regulator of the late phase of primary immune responses

NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth

Inflammatory bowel diseases involve the dynamic interplay of host genetics, microbiome and inflammatory response. Here, we report that NLRP12, a negative regulator of innate immunity, is reduced in human ulcerative colitis by comparing monozygotic twins and other patient cohorts. In parallel, Nlrp12-deficiency in mice caused increased colonic basal inflammation, leading to a less-diverse microbiome, loss of protective gut commensal strains (Lachnospiraceae) and increased colitogenic strains (Erysipelotrichaceae). Dysbiosis and colitis susceptibility associated with Nlrp12-deficency were reversed equally by treatment with antibodies targeting inflammatory cytokines or by administration of beneficial commensal Lachnospiraceae isolates. Fecal transplants from specific pathogen free reared mice into germ-free Nlrp12-deficient mice showed that NLRP12 and the microbiome each contribute to immune signaling that culminates in colon inflammation. These findings reveal a feed-forward loop where NLRP12 promotes specific commensals that can reverse gut inflammation, while cytokine blockade during NLRP12-deficiency can reverse dysbiosis