Peer Rejection and Emotion Development: The Role of Peer Rejection and Coming Out on Emotional Health among Gay and Bisexual Men

Gay and bisexual men experience a higher prevalence of negative mental health outcomes than their heterosexual counterparts. This study examines sexual identity milestone achievement—the age of first coming out to friends—for mediation on the association between childhood experiences of peer rejection and levels of emotion dysregulation in adulthood

Investigating investment in biopharmaceutical R&D

Recent studies have highlighted a reduction in projected financial returns associated with biopharmaceutical R&D, owing to decreased productivity, increases in costs and flattening revenue per new drug, prompting calls for dramatic revisions to R&D models. On the basis of previous financial modelling, the simplest hypothesis would be that new investment in such R&D should be minimal and focused on biologics in preference to small molecules, as the internal rate of return on investment for biologics projects has been reported to be higher (Nat. Rev. Drug Discov. 8, 609–610; 2009). We sought to discern how investors have been acting in recent years, and so examined investment trends in nascent public biopharmaceutical companies located in the United States by constructing a database of such companies that had US initial public offerings (IPOs) between 2010 and 2014 (see Supplementary information S1 (box) for details). We then analysed the characteristics of the 113 companies that met our inclusion criteria, including their corporate strategy and therapeutic modality focus. Here, we present the key findings from this analysis and discuss its implications based on our own financial modelling.United States. National Institutes of Health (NIANIH/R01AG043560

Sexual reproduction of human fungal pathogens

We review here recent advances in our understanding of sexual reproduction in fungal pathogens that commonly infect humans, including Candida albicans, Cryptococcus neoformans/gattii, and Aspergillus fumigatus. Where appropriate or relevant, we introduce findings on other species associated with human infections. In particular, we focus on rapid advances involving genetic, genomic, and population genetic approaches that have reshaped our view of how fungal pathogens evolve. Rather than being asexual, mitotic, and largely clonal, as was thought to be prevalent as recently as a decade ago, we now appreciate that the vast majority of pathogenic fungi have retained extant sexual, or parasexual, cycles. In some examples, sexual and parasexual unions of pathogenic fungi involve closely related individuals, generating diversity in the population but with more restricted recombination than expected from fertile, sexual, outcrossing and recombining populations. In other cases, species and isolates participate in global outcrossing populations with the capacity for considerable levels of gene flow. These findings illustrate general principles of eukaryotic pathogen emergence with relevance for other fungi, parasitic eukaryotic pathogens, and both unicellular and multicellular eukaryotic organisms

Reducing Youth Risk Behaviors Through Interactive Theater Intervention

The reduction of risk behaviors in secondary schools is a key concern for parents, teachers, and school administrators. School is one of the primary contexts of socialization for young people; thus, the investment in school-based programs to reduce risk behaviors is essential. In this study, we report on youth who participated in an intervention designed to improve decision-making skills based on positive youth development approaches. We examine changes in decision-making skills before and after involvement in the Teen Interactive Theater Education (TITE) program and retrospective self-assessment of change in knowledge, abilities, and beliefs as a result of participating in TITE (n = 127). Youth that reported increases in knowledge, abilities, and beliefs due to the intervention (n = 89) were more likely to think about the consequences of their decisions and list options before making a decision compared to their counterparts that reported less overall learning (n = 38). Implications for intervention research and stakeholders are discussed

Nonlinear instability in simulations of Large Plasma Device turbulence

Several simulations of turbulence in the Large Plasma Device (LAPD) [Gekelman et al., Rev. Sci. Instrum. 62, 2875 (1991)] are energetically analyzed and compared with each other and with the experiment. The simulations use the same model, but different axial boundary conditions. They employ either periodic, zero-value, zero-derivative, or sheath axial boundaries. The linear stability physics is different between the scenarios because the various boundary conditions allow the drift wave instability to access different axial structures, and the sheath boundary simulation contains a conducting wall mode instability which is just as unstable as the drift waves. Nevertheless, the turbulence in all the simulations is relatively similar because it is primarily driven by a robust nonlinear instability that is the same for all cases. The nonlinear instability preferentially drives k∥=0 potential energy fluctuations, which then three-wave couple to k∥≠0 potential energy fluctuations in order to access the adiabatic response to transfer their energy to kinetic energy fluctuations. The turbulence self-organizes to drive this nonlinear instability, which destroys the linear eigenmode structures, making the linear instabilities ineffective

Nonlinear instability in simulations of Large Plasma Device turbulence

Several simulations of turbulence in the Large Plasma Device (LAPD) [Gekelman et al., Rev. Sci. Instrum. 62, 2875 (1991)] are energetically analyzed and compared with each other and with the experiment. The simulations use the same model, but different axial boundary conditions. They employ either periodic, zero-value, zero-derivative, or sheath axial boundaries. The linear stability physics is different between the scenarios because the various boundary conditions allow the drift wave instability to access different axial structures, and the sheath boundary simulation contains a conducting wall mode instability which is just as unstable as the drift waves. Nevertheless, the turbulence in all the simulations is relatively similar because it is primarily driven by a robust nonlinear instability that is the same for all cases. The nonlinear instability preferentially drives k∥=0 potential energy fluctuations, which then three-wave couple to k∥≠0 potential energy fluctuations in order to access the adiabatic response to transfer their energy to kinetic energy fluctuations. The turbulence self-organizes to drive this nonlinear instability, which destroys the linear eigenmode structures, making the linear instabilities ineffective

Checkpoint Inhibitors in Nonsmall Cell Lung Cancer

Lung cancer remains the leading cause of cancer‐related deaths worldwide. The majority of NSCLC patients present with advanced stage disease. Lung cancer was once thought of as a low antigenicity cancer unlikely to benefit from immunotherapy, but has recently been found to have a high level of antigenicity. Moreover, a large body of research now exists to support both the safety and efficacy of immunotherapy in advanced stage NSCLC. The checkpoint inhibitors nivolumab, pembrolizumab, and atezolizumab are now approved by the U.S. Federal Drug Administration for second‐line treatment in advanced stage NSCLC. In addition to being efficacious, checkpoint inhibitors have a superior safety profile compared to previous standard of care, chemotherapy. Further trials are needed to investigate the checkpoint inhibitors’ role in combination treatment, first‐line treatment, and early stage disease

RRx-001 in Refractory Small-Cell Lung Carcinoma: A Case Report of a Partial Response after a Third Reintroduction of Platinum Doublets.

RRx-001 is a pan-active, systemically nontoxic epigenetic inhibitor under investigation in advanced non-small cell lung cancer, small-cell lung cancer and high-grade neuroendocrine tumors in a Phase II clinical trial entitled TRIPLE THREAT (NCT02489903), which reexposes patients to previously effective but refractory platinum doublets after treatment with RRx-001. The purpose of this case study is first to report a partial response to carboplatin and etoposide in a patient with small-cell lung cancer pretreated with RRx-001, indicating episensitization or resensitization by epigenetic mechanisms, and second to discuss the literature related to small-cell lung cancer and episensitization

Anti-CRISPR-mediated control of gene editing and synthetic circuits in eukaryotic cells.

Repurposed CRISPR-Cas molecules provide a useful tool set for broad applications of genomic editing and regulation of gene expression in prokaryotes and eukaryotes. Recent discovery of phage-derived proteins, anti-CRISPRs, which serve to abrogate natural CRISPR anti-phage activity, potentially expands the ability to build synthetic CRISPR-mediated circuits. Here, we characterize a panel of anti-CRISPR molecules for expanded applications to counteract CRISPR-mediated gene activation and repression of reporter and endogenous genes in various cell types. We demonstrate that cells pre-engineered with anti-CRISPR molecules become resistant to gene editing, thus providing a means to generate "write-protected" cells that prevent future gene editing. We further show that anti-CRISPRs can be used to control CRISPR-based gene regulation circuits, including implementation of a pulse generator circuit in mammalian cells. Our work suggests that anti-CRISPR proteins should serve as widely applicable tools for synthetic systems regulating the behavior of eukaryotic cells

Assessing Risk of Future Suicidality in Emergency Department Patients

Background. Emergency Departments (ED) are the first line of evaluation for patients at risk and in crisis, with or without overt suicidality (ideation, attempts). Currently employed triage and assessments methods miss some of the individuals who subsequently become suicidal. The Convergent Functional Information for Suicidality (CFI-S) 22 item checklist of risk factors, that does not ask directly about suicidal ideation, has demonstrated good predictive ability for suicidality in previous studies in psychiatric outpatients, but has not been tested in the real world-setting of emergency departments (EDs). Methods. We administered CFI-S prospectively to a convenience sample of consecutive ED patients. Median administration time was 3 minutes. Patients were also asked at triage about suicidal thoughts or intentions per standard ED suicide clinical screening (SCS), and the treating ED physician was asked to fill a physician gestalt visual analog scale (VAS) for likelihood of future suicidality spectrum events (SSE) (ideation, preparatory acts, attempts, completed suicide). We performed structured chart review and telephone follow-up at 6 months post index visit. Results. The median time to complete the CFI-S was three minutes (1st to 3rd quartile 3–6 minutes). Of the 338 patients enrolled, 45 (13.3%) were positive on the initial SCS, and 32 (9.5%) experienced a SSE in the 6 months follow-up. Overall, across genders, SCS had a modest diagnostic discrimination for future SSE (ROC AUC 0.63,). The physician VAS was better (AUC 0.76 CI 0.66–0.85), and the CFI-S was slightly higher (AUC 0.81, CI 0.76–0.87). The top CFI-S differentiating items were psychiatric illness, perceived uselessness, and social isolation. The top CFI-S items were family history of suicide, age, and past history of suicidal acts. Conclusions. Using CFI-S, or some of its items, in busy EDs may help improve the detection of patients at high risk for future suicidality