Transcriptional adaptation of Mycobacterium tuberculosis within macrophages: Insights into the phagosomal environment

Little is known about the biochemical environment in phagosomes harboring an infectious agent. To assess the state of this organelle we captured the transcriptional responses of Mycobacterium tuberculosis (MTB) in macrophages from wild-type and nitric oxide (NO) synthase 2–deficient mice before and after immunologic activation. The intraphagosomal transcriptome was compared with the transcriptome of MTB in standard broth culture and during growth in diverse conditions designed to simulate features of the phagosomal environment. Genes expressed differentially as a consequence of intraphagosomal residence included an interferon � – and NO-induced response that intensifies an iron-scavenging program, converts the microbe from aerobic to anaerobic respiration, and induces a dormancy regulon. Induction of genes involved in the activation and �-oxidation of fatty acids indicated that fatty acids furnish carbon and energy. Induction of �E-dependent, sodium dodecyl sulfate–regulated genes and genes involved in mycolic acid modification pointed to damage and repair of the cell envelope. Sentinel genes within the intraphagosomal transcriptome were induced similarly by MTB in the lungs of mice. The microbial transcriptome thus served as a bioprobe of the MTB phagosomal environment

Implementing risk stratification to the treatment of adolescent substance use among youth involved in the juvenile justice system: protocol of a hybrid type I trial

BACKGROUND: Youth involved in the juvenile justice system (YIJJ) have high rates of substance use problems; however, rates of YIJJ engagement in substance use services is low. Barriers to service engagement include lack of appropriate screening and connection to services by the juvenile justice system, as well as lack of resources for delivering evidence-based treatment in community-based settings. To address these barriers, this paper describes a protocol for a type 1 hybrid design to (1) implement universal substance use screening for YIJJ; (2) implement and evaluate the feasibility and effectiveness of a brief, three-session substance use interventions based in motivational interviewing for youth with mild/moderate substance use: Teen Intervene (an individual-based intervention); (3) implement ENCOMPASS, an evidence-based substance use intervention based in motivational enhancement and cognitive behavioral therapy for youth with severe substance use; and (4) evaluate facilitators and barriers to implementing these interventions for mild to severe substance use among YIJJ in community mental health centers (CMHC). METHODS/DESIGN: Using a hybrid type 1 clinical effectiveness-implementation design, we will collaborate with CMHCs and juvenile justice in two rural Indiana counties. Guided by the EPIS (exploration, preparation, implementation, sustainability) framework, we will measure factors that affect implementation of substance use screening in juvenile justice and implementation of substance use interventions in CMHCs utilizing self-reports and qualitative interviews with juvenile justice and CMHC staff pre- and post-implementation. YIJJ with mild/moderate substance use will receive a brief interventions and YIJJ with severe substance use will receive ENCOMPASS. We will measure the effectiveness of a brief and comprehensive intervention by assessing changes in substance use across treatment. We anticipate recruiting 160 YIJJ and their caregivers into the study. We will assess intervention outcomes utilizing baseline, 3-, and 6-month assessments. DISCUSSION: Findings have the potential to improve screening and intervention services for YIJJ

Symmetries and Interactions from Lattice QCD

Precision experimental tests of the Standard Model of particle physics (SM) are one of our best hopes for discovering what new physics lies beyond the SM (BSM). Key in the search for new physics is the connection between theory and experiment. Forging this connection for searches involving low-energy hadronic or nuclear environments requires the use of a non-perturbative theoretical tool, lattice QCD. We present two recent lattice QCD calculations by the CalLat collaboration relevant for new physics searches: the nucleon axial coupling, $g_A$, whose precise value as predicted by the SM could help point to new physics contributions to the so-called "neutron lifetime puzzle", and hadronic matrix elements of short-ranged operators relevant for neutrinoless double beta decay searches.Comment: Plenary talk presented CIPANP2018. 11 pages, 3 figure

Mortality of Youth Offenders Along a Continuum of Justice System Involvement

Introduction Black male youth are at high risk of homicide and criminal justice involvement. This study aimed to determine how early mortality among youth offenders varies based on race; gender; and the continuum of justice system involvement: arrest, detention, incarceration, and transfer to adult courts. Methods Criminal and death records of 49,479 youth offenders (ages 10–18 years at first arrest) in Marion County, Indiana, from January 1, 1999, to December 31, 2011, were examined. Statistical analyses were completed in November 2014. Results From 1999 to 2011 (aggregate exposure, 386,709 person-years), 518 youth offender deaths occurred. The most common cause of death was homicide (48.2%). The mortality rate of youth offenders was nearly 1.5 times greater than that among community youth (standardized mortality ratio, 1.48). The youth offender mortality rate varied depending on the severity of justice system involvement. Arrested youth had the lowest rate of mortality (90/100,000), followed by detained youth (165/100,000); incarcerated youth (216/100,000); and youth transferred to adult court (313/100,000). A proportional hazards model demonstrated that older age, male gender, and more severe justice system involvement 5 years post-arrest predicted shorter time to mortality. Conclusions Youth offenders face greater risk for early death than community youth. Among these, black male youth face higher risk of early mortality than their white male counterparts. However, regardless of race/ethnicity, mortality rates for youth offenders increase as youth involvement in the justice system becomes more protracted and severe. Thus, justice system involvement is a significant factor to target for intervention

Performativity, fabrication and trust: exploring computer-mediated moderation

Based on research conducted in an English secondary school, this paper explores computer mediated moderation as a performative tool. The Module Assessment Meeting (MAM) was the moderation approach under investigation. I mobilise ethnographic data generated by a key informant, and triangulated with that from other actors in the setting, in order to examine some of the meanings underpinning moderation within a performative environment. Drawing on the work of Ball (2003), Lyotard (1979) and Foucault (1977, 1979), I argue that in this particular case performativity has become entrenched in teachers’ day-to-day practices, and not only affects those practices but also teachers’ sense of self. I suggest that MAM represented performative and fabricated conditions and (re)defined what the key participant experienced as a vital constituent of her educational identities - trust. From examining the case in point, I hope to have illustrated for those interested in teachers’ work some of the implications of the interface between technology and performativity

Using XML and XSLT for flexible elicitation of mental-health risk knowledge

Current tools for assessing risks associated with mental-health problems require assessors to make high-level judgements based on clinical experience. This paper describes how new technologies can enhance qualitative research methods to identify lower-level cues underlying these judgements, which can be collected by people without a specialist mental-health background. Methods and evolving results: Content analysis of interviews with 46 multidisciplinary mental-health experts exposed the cues and their interrelationships, which were represented by a mind map using software that stores maps as XML. All 46 mind maps were integrated into a single XML knowledge structure and analysed by a Lisp program to generate quantitative information about the numbers of experts associated with each part of it. The knowledge was refined by the experts, using software developed in Flash to record their collective views within the XML itself. These views specified how the XML should be transformed by XSLT, a technology for rendering XML, which resulted in a validated hierarchical knowledge structure associating patient cues with risks. Conclusions: Changing knowledge elicitation requirements were accommodated by flexible transformations of XML data using XSLT, which also facilitated generation of multiple data-gathering tools suiting different assessment circumstances and levels of mental-health knowledge

Adverse Health Outcomes among U.S. Testicular Cancer Survivors after Cisplatin-Based Chemotherapy vs. Surgical Management

We evaluated for the first time adverse health outcomes (AHOs) among U.S. testicular cancer survivors (TCS) given chemotherapy (n = 381) vs. surgery-only patients (n = 98) managed at a single institution, accounting for non-treatment-related risk factors to delineate chemotherapy’s impact. Chemotherapy consisted largely of bleomycin-etoposide-cisplatin (BEP) administered in 3 or 4 cycles (BEPX3, n = 235; BEPX4, n = 82). Incidence of ≥ 3 AHOs was lowest in surgery-only TCS and increased with BEPX3, BEPX4 and other cisplatin-based regimens (12.2%, 40.8%, 52.5%, 54.8%; P<0.0001). Multivariate modeling assessed associations of risk factors and treatment with hearing impairment, tinnitus, peripheral neuropathy, and Raynaud phenomenon. Risk for each AHO significantly increased with both increasing chemotherapy burden (P < 0.0001) and selected modifiable risk factors (P < 0.05): hypertension (OR = 2.40) and noise exposure (OR ≥ 2.3) for hearing impairment; noise exposure for tinnitus (OR ≥ 1.69); peripheral vascular disease for neuropathy (OR = 8.72), and current smoking for Raynaud phenomenon (OR = 2.41). Clinicians should manage modifiable risk factors for AHOs among TCS

Neural-network analysis of Parton Distribution Functions from Ioffe-time pseudodistributions

International audienceWe extract two nonsinglet nucleon Parton Distribution Functions from lattice QCD data for reduced Ioffe-time pseudodistributions. We perform such analysis within the NNPDF framework, considering data coming from different lattice ensembles and dis- cussing in detail the treatment of the different source of systematics involved in the fit. We introduce a recipe for taking care of systematics and use it to perform our extraction of light-cone PDFs

Does tenure matter for occupant experiences of low-energy housing?

International policy settings are looking toward low-energy and near zero-energy homes as a solution to address environmental impacts, particularly anthropogenic climate change. There is increasing research evaluating sus-tainable housing developments from a technical and occupant perspective. One of the key determinants of household energy use is tenure. However, there is limited research which has looked at if tenure impacts on how oc-cupants experience low-energy homes. This paper contributes to the litera-ture by exploring three low-energy housing developments and exploring the role of tenure in relation to how the households experience the dwellings. The case studies demonstrate that social housing tenants have frustrations with a lack of control over what they could, or could not, do to their low-energy dwellings, in comparison to owner-occupier housing