Fluctuating epidemics on adaptive networks

A model for epidemics on an adaptive network is considered. Nodes follow an SIRS (susceptible-infective-recovered-susceptible) pattern. Connections are rewired to break links from non-infected nodes to infected nodes and are reformed to connect to other non-infected nodes, as the nodes that are not infected try to avoid the infection. Monte Carlo simulation and numerical solution of a mean field model are employed. The introduction of rewiring affects both the network structure and the epidemic dynamics. Degree distributions are altered, and the average distance from a node to the nearest infective increases. The rewiring leads to regions of bistability where either an endemic or a disease-free steady state can exist. Fluctuations around the endemic state and the lifetime of the endemic state are considered. The fluctuations are found to exhibit power law behavior.Comment: Submitted to Phys Rev

Projected temperature-related deaths in ten large U.S. metropolitan areas under different climate change scenarios.

BACKGROUND: There is an established U-shaped association between daily temperature and mortality. Temperature changes projected through the end of century are expected to lead to higher rates of heat-related mortality but also lower rates of cold-related mortality, such that the net change in temperature-related mortality will depend on location. OBJECTIVES: We quantified the change in heat-, cold-, and temperature-related mortality rates through the end of the century across 10 large US metropolitan areas. METHODS: We applied location-specific projections of future temperature from over 40 downscaled climate models to exposure-response functions relating daily temperature and mortality in 10 US metropolitan areas to estimate the change in temperature-related mortality rates in 2045-2055 and 2085-2095 compared to 1992-2002, under two greenhouse gas emissions scenarios (RCP 4.5 and 8.5). We further calculated the total number of deaths attributable to temperature in 1997, 2050, and 2090 in each metropolitan area, either assuming constant population or accounting for projected population growth. RESULTS: In each of the 10 metropolitan areas, projected future temperatures were associated with lower rates of cold-related deaths and higher rates of heat-related deaths. Under the higher-emission RCP 8.5 scenario, 8 of the 10 metropolitan areas are projected to experience a net increase in annual temperature-related deaths per million people by 2086-2095, ranging from a net increase of 627 (95% empirical confidence interval [eCI]: 239, 1018) deaths per million in Los Angeles to a net decrease of 59 (95% eCI: -485, 314) deaths per million in Boston. Applying these projected temperature-related mortality rates to projected population size underscores the large public health burden of temperature. CONCLUSIONS: Increases in the heat-related death rate are projected to outweigh decreases in the cold-related death rate in 8 out of 10 cities studied under a high emissions scenario. Adhering to a lower greenhouse gas emissions scenario has the potential to substantially reduce future temperature-related mortality

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Living with type 1 diabetes in Neno, Malawi: a qualitative study of self-management and experiences in care

Abstract Background The prevalence of type 1 diabetes (T1D) is increasing in low-income countries including Malawi. In this setting, care is frequently impacted by challenges in diagnosis and management. Access to high-quality T1D care remains limited in Malawi, with fairly low availability and high cost of insulin and other supplies and diagnostics, lack of T1D knowledge, and absence of readily accessible guidelines. In the Neno district, Partners In Health established advanced care clinics at district hospitals to provide comprehensive, free care for T1D and other noncommunicable diseases. Prior to this study, experiences in care for people living with T1D (PLWT1D) at these clinics remained unexplored. Here we examine the impact of living with T1D, knowledge and self-management of, and facilitators and barriers to T1D care in Neno District, Malawi. Methods We conducted a qualitative study utilizing behavior change theory that consisted of twenty-three semi-structured interviews conducted in Neno, Malawi in January 2021 with PLWT1D, their families, providers, and civil society members to explore the psychosocial and economic impact of living with T1D, T1D knowledge and self-management, and facilitators and barriers to accessing care. Interviews were analyzed thematically using a deductive approach. Results We found that PLWT1D had good knowledge and practice of self-management activities for T1D. Key facilitators to care identified by informants included extensive patient education and availability and provision of free insulin and supplies. Significant barriers included distance from health facilities, food insecurity, and low literacy/numeracy. Informants described T1D as having a notable psychosocial and economic impact on PWLT1D and their families, notably worrying about having a lifelong condition, high transportation costs, and reduced working ability. While home visits and transport refunds helped facilitate access to the clinic, informants reported the refunds as inadequate given high transport costs faced by patients. Conclusions T1D was found to have a significant impact on PLWT1D and their families. Our findings represent important areas of consideration in design and implementation of effective programs for treating PLWT1D in resource-limited settings. Facilitators to care identified by informants may be applicable and beneficial in similar settings, while persisting barriers represent areas for continued improvement in Neno

Second-Trimester Dilation and Evacuation: A Simulation-Based Team Training Curriculum

Introduction Despite the need for providers skilled in second-trimester dilation and evacuation (D&E) procedures, there are few second-trimester abortion training opportunities for OB/GYN residents and other health care trainees. Barriers to such training include restrictive state laws and institutional policies, lack of trained faculty, and limited procedural volume. Simulation-based D&E training is, therefore, a critical tool for OB/GYN residents and other medical professionals to achieve clinical competency. Methods This simulation for OB/GYN residents centers on a 29-year-old woman at 18 weeks gestation with intrauterine fetal demise, requiring learners to perform a second-trimester D&E and manage an unexpected postprocedural hemorrhage. We designed the simulation to be used with a high-fidelity mannequin. Personnel roles required for the simulation included an anesthesiologist, medical assistant, OR nurse, and two OB/GYN faculty. Learner performance was assessed using a pre- and postsimulation learner evaluation, a critical action checklist, and a focus group with simulation facilitators. Results Forty-nine residents participated over an 8-year period. Learners demonstrated improved competency performing a second-trimester D&E and increased confidence managing postprocedural hemorrhage after participating in this simulation. In addition, focus group participants reported that a majority of learners demonstrated confidence and effective communication with team members while performing in a decision-making role. Discussion In addition to improving learners’ clinical competency and surgical confidence for second-trimester D&E procedures, this simulation serves as a valuable instrument for the standardized assessment of learners’ performance, as well as an opportunity for all participants to practice teamwork and communication in a high-acuity setting