Kinetics and Determining Factors of the Virologic Response to Antiretrovirals during Pregnancy

HIV-infected pregnant women with undetectable plasma HIV RNA concentrations at delivery pose a minimal risk of vertical transmission. We studied the kinetics and the determinants of the virologic response to antiretroviral therapy in 117 consecutive pregnancies. Patients who initiated therapy during pregnancy had a VL decrease of 2 and 2.5 log10 after 4 and 24 weeks, respectively. Therapeutic drug monitoring (TDM) of the protease inhibitors administered in doses recommended for nonpregnant adults resulted in below-target concentrations in 29%, 35%, and 44% of 1st, 2nd, and 3rd trimester measurements, respectively, but low drug concentrations did not correlate with virologic failure. Demographic characteristics, antiretroviral experience prior to pregnancy, baseline VL, or use of specific antiretrovirals did not affect the virologic response. Adherence to ≥95% of prescribed doses and utilization of psychosocial services were associated with undetectable plasma HIV RNA at delivery. In conclusion, the virologic responses of pregnant and nonpregnant adults share similar charactersitics

Effectiveness of a digital cognitive behavior therapy-guided self-help intervention for eating disorders in college women: A cluster randomized clinical trial

Importance: Eating disorders (EDs) are common, serious psychiatric disorders on college campuses, yet most affected individuals do not receive treatment. Digital interventions have the potential to bridge this gap. Objective: To determine whether a coached, digital, cognitive behavior therapy (CBT) intervention improves outcomes for college women with EDs compared with referral to usual care. Design, Setting, and Participants: This cluster randomized trial was conducted from 2014 to 2018 at 27 US universities. Women with binge-purge EDs (with both threshold and subthreshold presentations) were recruited from enrolled universities. The 690 participants were followed up for up to 2 years after the intervention. Data analysis was performed from February to September 2019. Interventions: Universities were randomized to the intervention, Student Bodies-Eating Disorders, a digital CBT-guided self-help program, or to referral to usual care. Main Outcomes and Measures: The main outcome was change in overall ED psychopathology. Secondary outcomes were abstinence from binge eating and compensatory behaviors, as well as ED behavior frequencies, depression, anxiety, clinical impairment, academic impairment, and realized treatment access. Results: A total of 690 women with EDs (mean [SD] age, 22.12 [4.85] years; 414 [60.0%] White; 120 [17.4%] Hispanic; 512 [74.2%] undergraduates) were included in the analyses. For ED psychopathology, there was a significantly greater reduction in the intervention group compared with the control group at the postintervention assessment (β [SE], -0.44 [0.10]; d = -0.40; t1387 = -4.23; P \u3c .001), as well as over the follow-up period (β [SE], -0.39 [0.12]; d = -0.35; t1387 = -3.30; P \u3c .001). There was not a significant difference in abstinence from any ED behaviors at the postintervention assessment (odds ratio, 1.48; 95% CI, 0.48-4.62; P = .50) or at follow-up (odds ratio, 1.51; 95% CI, 0.63-3.58; P = .36). Compared with the control group, the intervention group had significantly greater reductions in binge eating (rate ratio, 0.82; 95% CI, 0.70-0.96; P = .02), compensatory behaviors (rate ratio, 0.68; 95% CI, 0.54-0.86; P \u3c .001), depression (β [SE], -1.34 [0.53]; d = -0.22; t1387 = -2.52; P = .01), and clinical impairment (β [SE], -2.33 [0.94]; d = -0.21; t1387 = -2.49; P = .01) at the postintervention assessment, with these gains sustained through follow-up for all outcomes except binge eating. Groups did not differ in terms of academic impairment. The majority of intervention participants (318 of 385 participants [83%]) began the intervention, whereas only 28% of control participants (76 of 271 participants with follow-up data available) sought treatment for their ED (odds ratio, 12.36; 95% CI, 8.73-17.51; P \u3c .001). Conclusions and Relevance: In this cluster randomized clinical trial comparing a coached, digital CBT intervention with referral to usual care, the intervention was effective in reducing ED psychopathology, compensatory behaviors, depression, and clinical impairment through long-term follow-up, as well as realizing treatment access. No difference was found between the intervention and control groups for abstinence for all ED behaviors or academic impairment. Given its scalability, a coached, digital, CBT intervention for college women with EDs has the potential to address the wide treatment gap for these disorders. Trial Registration: ClinicalTrials.gov Identifier: NCT02076464

Game-Play Breakdowns and Breakthroughs: Exploring the Relationship Between Action, Understanding, and Involvement

Game developers have to ensure their games are appealing to, and playable by, a range of people. However, although there has been interest in the game-play experience, we know little about how learning relates to player involvement. This is despite challenge being an integral part of game-play, providing players with potential opportunities to learn. This article reports on a multiple case-study approach that explored how learning and involvement come together in practice. Participants consisted of a mix of gamers and casual players. Data included interviews, multiple observations of game-play, postplay cued interviews, and diary entries. A set of theoretical claims representing suggested relationships between involvement and learning were developed on the basis of previous literature; these were then assessed through a critical examination of the data set. The resulting theory is presented as 14 refined claims that relate to micro and macro involvement; breakdowns and breakthroughs in action, understanding, and involvement; progress; and agency, meaning and compelling game-play. The claims emphasize how players experience learning via breakthroughs in understanding, where involvement is increased when the player feels responsible for progress. Supporting the relationship between learning and involvement is important for ensuring the success of commercial and educational games

Genomic hallmarks and therapeutic implications of G0 cell cycle arrest in cancer

BACKGROUND: Therapy resistance in cancer is often driven by a subpopulation of cells that are temporarily arrested in a non-proliferative G0 state, which is difficult to capture and whose mutational drivers remain largely unknown. RESULTS: We develop methodology to robustly identify this state from transcriptomic signals and characterise its prevalence and genomic constraints in solid primary tumours. We show that G0 arrest preferentially emerges in the context of more stable, less mutated genomes which maintain TP53 integrity and lack the hallmarks of DNA damage repair deficiency, while presenting increased APOBEC mutagenesis. We employ machine learning to uncover novel genomic dependencies of this process and validate the role of the centrosomal gene CEP89 as a modulator of proliferation and G0 arrest capacity. Lastly, we demonstrate that G0 arrest underlies unfavourable responses to various therapies exploiting cell cycle, kinase signalling and epigenetic mechanisms in single-cell data. CONCLUSIONS: We propose a G0 arrest transcriptional signature that is linked with therapeutic resistance and can be used to further study and clinically track this state

Urbanization affects oak-pathogen interactions across spatial scales

The world is rapidly urbanizing, thereby transforming natural landscapes and changing the abundance and distribution of organisms. However, insights into the effects of urbanization on species interactions, and plant-pathogen interactions in particular, are lacking. We investigated the effects of urbanization on powdery mildew infection on Quercus robur at continental and within-city scales. At the continental scale, we compared infection levels between urban and rural areas of different-sized cities in Europe, and investigated whether plant traits, climatic variables and CO2 emissions mediated the effect of urbanization on infection levels. Within one large city (Stockholm, Sweden), we further explored whether local habitat features and spatial connectivity influenced infection levels during multiple years. At the continental scale, infection severity was consistently higher on trees in urban than rural areas, with some indication that temperature mediated this effect. Within Stockholm city, temperature had no effect, while local accumulation of leaf litter negatively affected powdery mildew incidence in one out of three years, and more connected trees had lower infection levels. This study is the first to describe the effects of urbanization on plant-pathogen interactions both within and among cities, and to uncover the potential mechanisms behind the observed patterns at each scale.Peer reviewe

Adapting a mobile app to support patients with anorexia nervosa following post-acute care: perspectives from eating disorder treatment center stakeholders

Introduction Anorexia nervosa (AN) is a harmful, life-threatening illness. Patients with severe AN often receive acute treatment but, upon discharge, experience high relapse rates. Evidence-based, outpatient treatment following acute care is critical to preventing relapse; however, numerous barriers (e.g., location, financial limitations, low availability of providers) preclude individuals from accessing treatment. mHealth technologies may help to address these barriers, but research on such digital approaches for those with AN is limited. Further, such technologies should be developed with all relevant stakeholder input considered from the outset. As such, the present study aimed to garner feedback from eating disorder (ED) treatment center providers on (1) the process of discharging patients to outpatient services, (2) their experiences with technology as a treatment tool, and (3) how future mHealth technologies may be harnessed to offer the most benefit to patients in the post-acute period. Methods Participants (N = 11, from 7 ED treatment centers across the United States) were interviewed. To analyze the data for this study, each interview was manually transcribed and analyzed using components of Braun and Clarke's six-phase thematic analysis framework (Braun & Clarke, 2006). Results Participants indicated proactively securing outpatient care for their patients, but mentioned several barriers their patients face in accessing evidence-based ED treatment. All participants had some experience using various technologies for treatment (e.g., teletherapy, self-monitoring apps), and mentioned a high level of interest in the development of a new app to be used by patients recently discharged from acute treatment for AN. Participants also offered suggestions of effective and relevant content for a potential app and adjunctive social networking component for post-acute care of AN. Discussion Overall, participants expressed positive attitudes toward the integration of an app into the care flow, suggesting the high potential benefit of harnessing technology to support individuals recovering from AN

Development and validation of a short version of the Partnership Self-Assessment Tool (PSAT) among professionals in Dutch disease-management partnerships

Background: The extent to which partnership synergy is created within quality improvement programmes in the Netherlands is unknown. In this article, we describe the psychometric testing of the Partnership Self-Assessment Tool (PSAT) among professionals in twenty-two disease-management partnerships participating in quality improvement projects focused on chronic care in the Netherlands. Our objectives are to validate the PSAT in the Netherlands and to reduce the number of items of the original PSAT while maintaining validity and reliability. Methods. The Dutch version of the PSAT was tested in twenty-two disease-management partnerships with 218 professionals. We tested the instrument by means of structural equation modelling, and examined its validity and reliability. Results: After eliminating 14 items, the confirmatory factor analyses revealed good indices of fit with the resulting 15-item PSAT-Short version (PSAT-S). Internal consistency as represented by Cronbach's alpha ranged from acceptable (0.75) for the 'efficiency' subscale to excellent for the 'leadership' subscale (0.87). Convergent validity was provided with high correlations of the partnership dimensions and partnership synergy (ranged from 0.512 to 0.609) and high correlations with chronic illness care (ranged from 0.447 to 0.329). Conclusion: The psychometric properties and convergent validity of the PSAT-S were satisfactory rendering it a valid and reliable instrument for assessing partnership syne

Association of Impulsivity and Polymorphic MicroRNA-641 Target Sites in the SNAP-25 Gene.

Impulsivity is a personality trait of high impact and is connected with several types of maladaptive behavior and psychiatric diseases, such as attention deficit hyperactivity disorder, alcohol and drug abuse, as well as pathological gambling and mood disorders. Polymorphic variants of the SNAP-25 gene emerged as putative genetic components of impulsivity, as SNAP-25 protein plays an important role in the central nervous system, and its SNPs are associated with several psychiatric disorders. In this study we aimed to investigate if polymorphisms in the regulatory regions of the SNAP-25 gene are in association with normal variability of impulsivity. Genotypes and haplotypes of two polymorphisms in the promoter (rs6077690 and rs6039769) and two SNPs in the 3' UTR (rs3746544 and rs1051312) of the SNAP-25 gene were determined in a healthy Hungarian population (N = 901) using PCR-RFLP or real-time PCR in combination with sequence specific probes. Significant association was found between the T-T 3' UTR haplotype and impulsivity, whereas no association could be detected with genotypes or haplotypes of the promoter loci. According to sequence alignment, the polymorphisms in the 3' UTR of the gene alter the binding site of microRNA-641, which was analyzed by luciferase reporter system. It was observed that haplotypes altering one or two nucleotides in the binding site of the seed region of microRNA-641 significantly increased the amount of generated protein in vitro. These findings support the role of polymorphic SNAP-25 variants both at psychogenetic and molecular biological levels

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo