Weather Regulates Location, Timing, and Intensity of Dengue Virus Transmission between Humans and Mosquitoes.

BACKGROUND: Dengue is one of the most aggressively expanding mosquito-transmitted viruses. The human burden approaches 400 million infections annually. Complex transmission dynamics pose challenges for predicting location, timing, and magnitude of risk; thus, models are needed to guide prevention strategies and policy development locally and globally. Weather regulates transmission-potential via its effects on vector dynamics. An important gap in understanding risk and roadblock in model development is an empirical perspective clarifying how weather impacts transmission in diverse ecological settings. We sought to determine if location, timing, and potential-intensity of transmission are systematically defined by weather. METHODOLOGY/PRINCIPAL FINDINGS: We developed a high-resolution empirical profile of the local weather-disease connection across Peru, a country with considerable ecological diversity. Applying 2-dimensional weather-space that pairs temperature versus humidity, we mapped local transmission-potential in weather-space by week during 1994-2012. A binary classification-tree was developed to test whether weather data could classify 1828 Peruvian districts as positive/negative for transmission and into ranks of transmission-potential with respect to observed disease. We show that transmission-potential is regulated by temperature-humidity coupling, enabling epidemics in a limited area of weather-space. Duration within a specific temperature range defines transmission-potential that is amplified exponentially in higher humidity. Dengue-positive districts were identified by mean temperature >22°C for 7+ weeks and minimum temperature >14°C for 33+ weeks annually with 95% sensitivity and specificity. In elevated-risk locations, seasonal peak-incidence occurred when mean temperature was 26-29°C, coincident with humidity at its local maximum; highest incidence when humidity >80%. We profile transmission-potential in weather-space for temperature-humidity ranging 0-38°C and 5-100% at 1°C x 2% resolution. CONCLUSIONS/SIGNIFICANCE: Local duration in limited areas of temperature-humidity weather-space identifies potential locations, timing, and magnitude of transmission. The weather-space profile of transmission-potential provides needed data that define a systematic and highly-sensitive weather-disease connection, demonstrating separate but coupled roles of temperature and humidity. New insights regarding natural regulation of human-mosquito transmission across diverse ecological settings advance our understanding of risk locally and globally for dengue and other mosquito-borne diseases and support advances in public health policy/operations, providing an evidence-base for modeling, predicting risk, and surveillance-prevention planning.

Application of mobile teledermatology for skin cancer screening.

BACKGROUND: With advancements in mobile technology, cellular phone-based store-and-forward teledermatology may be applied to skin cancer screening. OBJECTIVE: We sought to determine diagnostic and management concordance between in-person and teledermatology evaluations for patients at skin cancer screening whose clinical images and history were transmitted through mobile phones. METHODS: A total of 86 patients with 137 skin lesions presented to a skin cancer screening event in California. These patients' clinical history and skin images were captured by a software-enabled mobile phone. Patients were assessed separately by an in-person dermatologist and a teledermatologist, who evaluated the mobile phone-transmitted history and images. Diagnostic and management concordance was determined between the in-person and teledermatology evaluations. RESULTS: The primary categorical diagnostic concordance was 82% between the in-person dermatologist and the teledermatologist (95% confidence interval 0.73-0.89), with a Kappa coefficient of 0.62 indicating good agreement. The aggregated diagnostic concordance between the in-person dermatologist and the teledermatologist was 62% (95% confidence interval 0.51-0.71), with Kappa coefficient of 0.60 indicating good agreement. Management concordance between the in-person dermatologist and the teledermatologist was 81% (95% confidence interval 0.72-0.88), with a Kappa coefficient of 0.57, which indicates moderate agreement between the dermatologists. Multivariate analysis showed that older age and presentation of atypical nevus were significantly associated with disagreement in diagnosis between the teledermatologist and in-person dermatologist, after adjusting for other factors. LIMITATIONS: Dermatoscopic images were not captured via mobile phones, which might improve diagnostic accuracy. CONCLUSION: Mobile teledermatology using cellular phones is an innovative and convenient modality of providing dermatologic consultations for skin cancer screening.

Equilibrium conformational dynamics in an RNA tetraloop from massively parallel molecular dynamics.

Conformational equilibrium within the ubiquitous GNRA tetraloop motif was simulated at the ensemble level, including 10 000 independent all-atom molecular dynamics trajectories totaling over 110 micros of simulation time. This robust sampling reveals a highly dynamic structure comprised of 15 conformational microstates. We assemble a Markov model that includes transitions ranging from the nanosecond to microsecond timescales and is dominated by six key loop conformations that contribute to fluctuations around the native state. Mining of the Protein Data Bank provides an abundance of structures in which GNRA tetraloops participate in tertiary contact formation. Most predominantly observed in the experimental data are interactions of the native loop structure within the minor groove of adjacent helical regions. Additionally, a second trend is observed in which the tetraloop assumes non-native conformations while participating in multiple tertiary contacts, in some cases involving multiple possible loop conformations. This tetraloop flexibility can act to counterbalance the energetic penalty associated with assuming non-native loop structures in forming tertiary contacts. The GNRA motif has thus evolved not only to readily participate in simple tertiary interactions involving native loop structure, but also to easily adapt tetraloop secondary conformation in order to participate in larger, more complex tertiary interactions.