Hamiltonian analysis of subcritical stochastic epidemic dynamics

We extend a technique of approximation of the long-term behavior of a supercritical stochastic epidemic model, using the WKB approximation and a Hamiltonian phase space, to the subcritical case. The limiting behavior of the model and approximation are qualitatively different in the subcritical case, requiring a novel analysis of the limiting behavior of the Hamiltonian system away from its deterministic subsystem. This yields a novel, general technique of approximation of the quasistationary distribution of stochastic epidemic and birth-death models, and may lead to techniques for analysis of these models beyond the quasistationary distribution. For a classic SIS model, the approximation found for the quasistationary distribution is very similar to published approximations but not identical. For a birth-death process without depletion of susceptibles, the approximation is exact. Dynamics on the phase plane similar to those predicted by the Hamiltonian analysis are demonstrated in cross-sectional data from trachoma treatment trials in Ethiopia, in which declining prevalences are consistent with subcritical epidemic dynamics

Continuously tunable modulation scheme for precision control of optical cavities with variable detuning

We present a scheme for locking optical cavities with arbitrary detuning by many linewidths from resonance using an electro-optic modulator that can provide arbitrary ratios of amplitude-to-phase modulation. We demonstrate our scheme on a Fabry–Perot cavity, and show that a well-behaved linear error signal can be obtained by demodulating the reflected light from a cavity that is detuned by several linewidths.National Science Foundation (U.S.) (PHY-0757058

Short-term leprosy forecasting from an expert opinion survey.

We conducted an expert survey of leprosy (Hansen's Disease) and neglected tropical disease experts in February 2016. Experts were asked to forecast the next year of reported cases for the world, for the top three countries, and for selected states and territories of India. A total of 103 respondents answered at least one forecasting question. We elicited lower and upper confidence bounds. Comparing these results to regression and exponential smoothing, we found no evidence that any forecasting method outperformed the others. We found evidence that experts who believed it was more likely to achieve global interruption of transmission goals and disability reduction goals had higher error scores for India and Indonesia, but lower for Brazil. Even for a disease whose epidemiology changes on a slow time scale, forecasting exercises such as we conducted are simple and practical. We believe they can be used on a routine basis in public health

Key questions for the evaluation of anti-amyloid immunotherapies for Alzheimer’s disease

The clinical benefit associated with anti-amyloid immunotherapies, a new class of drugs for the treatment of Alzheimer’s disease, is predicated on their ability to modify disease course by lowering brain amyloid levels. At the time of writing, two amyloid-lowering antibodies, aducanumab and lecanemab, have obtained United States Food and Drug Administration accelerated approval, with further agents of this class in the Alzheimer’s disease treatment pipeline. Based on limited published clinical trial data to date, regulators, payors and physicians will need to assess their efficacy, clinical effectiveness and safety, as well as cost and accessibility. We propose that attention to three important questions related to treatment efficacy, clinical effectiveness and safety should guide evidence-based consideration of this important class of drugs. These are: (1) Were trial statistical analyses appropriate and did they convincingly support claims of efficacy? (2) Do reported treatment effects outweigh safety concerns and are they generalizable to a representative clinical population of people with Alzheimer’s disease? and (3) Do the data convincingly demonstrate disease course modification, suggesting that increasing clinical benefits beyond the duration of the trials are likely? We suggest specific approaches to interpreting trial results for these drugs and highlight important areas of uncertainty where additional data and a cautious interpretation of existing results is warranted. Safe, effective and accessible treatments for Alzheimer’s disease are eagerly awaited by millions of patients and their caregivers worldwide. While amyloid-targeting immunotherapies may be promising disease-modifying Alzheimer’s disease treatments, rigorous and unbiased assessment of clinical trial data is critical to regulatory decision-making and subsequently determining their provision and utility in routine clinical practice. Our recommendations provide a framework for evidence-based appraisal of these drugs by regulators, payors, physicians and patients

Correction: Short-term leprosy forecasting from an expert opinion survey.

[This corrects the article DOI: 10.1371/journal.pone.0182245.]

Mathematical Models of Vaccine-Preventable Disease in California

In chapter 1, using a Galton-Watson branching-process analysis, we characterize differences in measles transmission by estimating the association between genotype and the reproduction number among post-elimination California measles cases. Genotype B3 is found to be a significant predictor of transmissibility.In chapter 2, we determine whether data from FDA-cleared wired and Bluetooth smart thermometers sold by a San Francisco-based company aid influenza forecasting efforts. We compare this smart thermometer data to regional influenza and ILI surveilance data from the California Department of Public Health. We evaluated the correlation between the regional California surveillance data and smart thermometer data, tested the hypothesis that smart thermometer readings and symptom reports provide regionally specific predictions, and determined whether smart thermometer and mobile application improved disease forecasts. Our results are consistent with the hypothesis that smart thermometer readings and symptom reports reflect underlying disease transmission in California. Data from such cloud-based devices could supplement syndromic influenza surveillance data.In chapter 3, we examine whether changes in varicella transmissibility may have occurred following the change from one- to two-dose vaccination scheduling in 2007. Following the change in ACIP recommendations for varicella vaccination in 2007, the median outbreak size decreased. However, while the number of outbreaks has continued to decrease following 2008, we do not find evidence that the distribution of sizes has changed since 2008. Using insights from branching process models assuming both subcritical and supercritical transmission and with and without depletion of susceptibles, we cannot rule out that varicella transmission is supercritical in school-based settings