Rabies Surveillance Identifies Potential Risk Corridors and Enables Management Evaluation

Intensive efforts are being made to eliminate the raccoon variant of rabies virus (RABV) from the eastern United States and Canada. The United States Department of Agriculture (USDA) Wildlife Services National Rabies Management Program has implemented enhanced rabies surveillance (ERS) to improve case detection across the extent of the raccoon oral rabies vaccination (ORV) management area. We evaluated ERS and public health surveillance data from 2006 to 2017 in three northeastern USA states using a dynamic occupancy modeling approach. Our objectives were to examine potential risk corridors for RABV incursion from the U.S. into Canada, evaluate the effectiveness of ORV management strategies, and identify surveillance gaps. ORV management has resulted in a decrease in RABV cases over time within vaccination zones (from occupancy (ψ) of 0.60 standard error (SE) = 0.03 in the spring of 2006 to ψ of 0.33 SE = 0.10 in the spring 2017). RABV cases also reduced in the enzootic area (from ψ of 0.60 SE = 0.03 in the spring of 2006 to ψ of 0.45 SE = 0.05 in the spring 2017). Although RABV occurrence was related to habitat type, greater impacts were associated with ORV and trap–vaccinate–release (TVR) campaigns, in addition to seasonal and yearly trends. Reductions in RABV occupancy were more pronounced in areas treated with Ontario Rabies Vaccine Bait (ONRAB) compared to RABORAL V-RG®. Our approach tracked changes in RABV occurrence across space and time, identified risk corridors for potential incursions into Canada, and highlighted surveillance gaps, while evaluating the impacts of management actions. Using this approach, we are able to provide guidance for future RABV management

Baroreflex Sensitivity is Impaired in Athletes Following a Sports-Related Concussion

Sport-related concussions are a major public health concern, with approximately 3.8 million incidences occurring annually in the United States alone. Autonomic nervous system (ANS) dysfunction is implicated in early and later stages of sports-related concussion recovery. Arterial baroreflex, a crucial mechanism by which the ANS controls short-term fluctuations in blood pressure, remains understudied in this population. PURPOSE: Examine baroreflex sensitivity (BRS) at rest during acute and sub-acute recovery phases following a sport-related concussion in collegiate athletes in comparison to non-injured athletes as controls. METHODS: Athletes (20±1 years) with sports-related concussions were tested on days 3 (N=13), 21 (N=13), and 90 (N=11) following the injury. Control athletes (N=12) were assessed at one time-point. Continuous arterial blood pressure (finger photoplethysmography) and R-R intervals (3-lead electrocardiogram) were obtained at rest for 6 minutes and while subjects were seated in an upright position. BRS was estimated with transfer function analysis to assess the fluctuations in systolic blood pressure and R-R intervals during the time period. Transfer gain in the low-frequency range (0.05– 0.15 Hz) quantified the magnitude of the relationship between changes in systolic blood pressure and R-R interval. Therefore, higher gain indicates higher BRS. A linear mixed model was used to examine symptoms and transfer function variables between the controls and the concussed athletes at the three time points. RESULTS: As anticipated, symptoms were worse on day-3 and resolved during the day-21 sub-acute phase. BRS was lower on day-3 (0.656±0.2U; p=0.003), day-21 (0.711±0.29U; p=0.013), and day-90 (0.77±0.27; p=0.04) following the injury compared to the controls (1.05±0.3U). CONCLUSION: The findings confirm impairments in baroreflex sensitivity during the acute and subacute recovery phases following a concussion despite symptom resolution. Blunted baroreflex sensitivity following injury may position athletes in a vulnerable situation while performing tasks that elicit sudden changes in blood pressure on and off the field

Using Global Positioning System Technology to Manage Human-Black Bear Incidents at Yosemite National Park

Managing human–bear (Ursus spp.) incidents is a top management priority in national parks inhabited by bears. Yosemite National Park (Yosemite), located in the Sierra Nevada in California, USA, receives up to 5 million visitors annually. It is also home to 300–500 black bears (U. americanus). Yosemite has an extensive history of black bear research, educational programs, and innovative solutions for reducing human–bear incidents. Despite this, human–bear incidents peaked in 1998 at 1,584. The resulting political fallout led to Yosemite receiving funds to expand its bear management program, including increasing its staffing and garbage pick-up, and improving the park’s bear-resistant infrastructure. In 2011, Yosemite reached a milestone when it recorded only 114 human–bear incidents—a 93% decrease from the 1998 high. To sustain this lower level of incidents while facing shrinking budgets and increasing visitation, bear managers turned to more modern technology. From 2014–2018, we evaluated the effectiveness of using global positioning system (GPS) collars to manage bears more proactively, increase staff and public engagement with bears, and gain insight into the bears’ spatial and temporal movements. The GPS collars were effective in achieving these goals, while also improving both our time management and our communication with park management. By the end of November 2018, Yosemite had recorded only 22 human–bear incidents—a 99% decrease from the 1998 high. The GPS collars are now an integral part of the Yosemite bear management program. We provide recommendations on how GPS technology may help other parks reduce human–bear incidents

Hypocotyl Transcriptome Reveals Auxin Regulation of Growth-Promoting Genes through GA-Dependent and -Independent Pathways

Many processes critical to plant growth and development are regulated by the hormone auxin. Auxin responses are initiated through activation of a transcriptional response mediated by the TIR1/AFB family of F-box protein auxin receptors as well as the AUX/IAA and ARF families of transcriptional regulators. However, there is little information on how auxin regulates a specific cellular response. To begin to address this question, we have focused on auxin regulation of cell expansion in the Arabidopsis hypocotyl. We show that auxin-mediated hypocotyl elongation is dependent upon the TIR1/AFB family of auxin receptors and degradation of AUX/IAA repressors. We also use microarray studies of elongating hypocotyls to show that a number of growth-associated processes are activated by auxin including gibberellin biosynthesis, cell wall reorganization and biogenesis, and others. Our studies indicate that GA biosynthesis is required for normal response to auxin in the hypocotyl but that the overall transcriptional auxin output consists of PIF-dependent and -independent genes. We propose that auxin acts independently from and interdependently with PIF and GA pathways to regulate expression of growth-associated genes in cell expansion

Population sequencing data reveal a compendium of mutational processes in human germline

Mechanistic processes underlying human germline mutations remain largely unknown.Variation in mutation rate and spectra along the genome is informative about the biological mechanisms. We statistically decompose this variation into separate processes using a blind source separation technique. The analysis of a large-scale whole genome sequencing dataset (TOPMed) reveals nine processes that explain the variation in mutation properties between loci. Seven of these processes lend themselves to a biological interpretation. One process is driven by bulky DNA lesions that resolve asymmetrically with respect to transcription and replication. Two processes independently track direction of replication fork and replication timing. We identify a mutagenic effect of active demethylation primarily acting in regulatory regions. We also demonstrate that a recently discovered mutagenic process specific to oocytes can be localized solely from population sequencing data. This process is spread across all chromosomes and is highly asymmetric with respect to the direction of transcription, suggesting a major role of DNA damage

Associations between polygenic risk for psychiatric disorders and substance involvement

Despite evidence of substantial comorbidity between psychiatric disorders and substance involvement, the extent to which common genetic factors contribute to their co-occurrence remains understudied. In the current study, we tested for associations between polygenic risk for psychiatric disorders and substance involvement (i.e., ranging from ever-use to severe dependence) among 2573 non-Hispanic European-American participants from the Study of Addiction: Genetics and Environment. Polygenic risk scores (PRS) for cross-disorder psychopathology (CROSS) were generated based on the Psychiatric Genomics Consortium’s Cross-Disorder meta-analysis and then tested for associations with a factor representing general liability to alcohol, cannabis, cocaine, nicotine, and opioid involvement (GENSUB). Follow-up analyses evaluated specific associations between each of the 5 psychiatric disorders which comprised CROSS—attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (AUT), bipolar disorder (BIP), major depressive disorder (MDD), and schizophrenia (SCZ)—and involvement with each component substance included in GENSUB. CROSS PRS explained 1.10% of variance in GENSUB in our sample (p<0.001). After correction for multiple testing in our follow-up analyses of polygenic risk for each individual disorder predicting involvement with each component substance, associations remained between: A) MDD PRS and non-problem cannabis use, B) MDD PRS and severe cocaine dependence, C) SCZ PRS and non-problem cannabis use and severe cannabis dependence, and D) SCZ PRS and severe cocaine dependence. These results suggest that shared covariance from common genetic variation contributes to psychiatric and substance involvement comorbidity

Rabies Surveillance Identifies Potential Risk Corridors and Enables Management Evaluation

Intensive efforts are being made to eliminate the raccoon variant of rabies virus (RABV) from the eastern United States and Canada. The United States Department of Agriculture (USDA) Wildlife Services National Rabies Management Program has implemented enhanced rabies surveillance (ERS) to improve case detection across the extent of the raccoon oral rabies vaccination (ORV) management area. We evaluated ERS and public health surveillance data from 2006 to 2017 in three northeastern USA states using a dynamic occupancy modeling approach. Our objectives were to examine potential risk corridors for RABV incursion from the U.S. into Canada, evaluate the effectiveness of ORV management strategies, and identify surveillance gaps. ORV management has resulted in a decrease in RABV cases over time within vaccination zones (from occupancy (ψ) of 0.60 standard error (SE) = 0.03 in the spring of 2006 to ψ of 0.33 SE = 0.10 in the spring 2017). RABV cases also reduced in the enzootic area (from ψ of 0.60 SE = 0.03 in the spring of 2006 to ψ of 0.45 SE = 0.05 in the spring 2017). Although RABV occurrence was related to habitat type, greater impacts were associated with ORV and trap–vaccinate–release (TVR) campaigns, in addition to seasonal and yearly trends. Reductions in RABV occupancy were more pronounced in areas treated with Ontario Rabies Vaccine Bait (ONRAB) compared to RABORAL V-RG®. Our approach tracked changes in RABV occurrence across space and time, identified risk corridors for potential incursions into Canada, and highlighted surveillance gaps, while evaluating the impacts of management actions. Using this approach, we are able to provide guidance for future RABV management

Evaluation of Contingency Actions to Control the Spread of Raccoon Rabies in Ohio and Virginia

The raccoon (Procyon lotor) variant of the rabies virus (RRV) is enzootic in the eastern United States and oral rabies vaccination (ORV) is the primary strategy to prevent and control landscape spread. Breaches of ORV management zones occasionally occur, and emergency “contingency” actions may be implemented to enhance local control. Contingency actions are an integral part of landscape-scale wildlife rabies management but can be very costly and routinely involve enhanced rabies surveillance (ERS) around the index case. We investigated two contingency actions in Ohio (2017–2019 and 2018–2021) and one in Virginia (2017–2019) using a dynamic, multi-method occupancy approach to examine relationships between specific management actions and RRV occurrence, including whether ERS was sufficient around the index case. The RRV occupancy was assessed seasonally at 100-km2 grids and we examined relationships across three spatial scales (regional management zone, RRV free regions, and local contingency areas). The location of a grid relative to the ORV management zone was the strongest predictor of RRV occupancy at the regional scale. In RRV free regions, the neighbor effect and temporal variability were most important in influencing RRV occupancy. Parenteral (hand) vaccination of raccoons was important across all three contingency action areas, but more influential in the Ohio contingency action areas where more raccoons were hand vaccinated. In the Virginia contingency action area, ORV strategies were as important in reducing RRV occupancy as a hand vaccination strategy. The management action to trap, euthanize, and test (TET) raccoons was an important method to increase ERS, yet the impacts of TET on RRV occupancy are not clear. The probability of detecting additional cases of RRV was exceptionally high (\u3e 0.95) during the season the index case occurred. The probability of detecting RRV through ERS declined in the seasons following initial TET efforts but remained higher after the contingency action compared to the ERS detection probabilities prior to index case incidence. Local RRV cases were contained within one year and eliminated within 2–3 years of each contingency action

Symptom Clusters in Acute Myocardial Infarction: A Secondary Data Analysis

Background: Early recognition of acute myocardial infarction (AMI) symptoms and reduced time to treatment may reduce morbidity and mortality. People having AMI experience a constellation of symptoms, but the common constellations or clusters of symptoms have yet to be identified. Objectives: To identify clusters of symptoms that represent AMI. Methods: This was a secondary data analysis of nine descriptive, cross-sectional studies that included data from 1,073 people having AMI in the United States and England. Data were analyzed using latent class cluster analysis, an atheoretical method that uses only information contained in the data. Results: Five distinct clusters of symptoms were identified. Age, race, and sex were statistically significant in predicting cluster membership. None of the symptom clusters described in this analysis included all of the symptoms that are considered typical. In one cluster, subjects had only a moderate to low probability of experiencing any of the symptoms analyzed. Discussion: Symptoms of AMI occur in clusters, and these clusters vary among persons. None of the clusters identified in this study included all of the symptoms that are included typically as symptoms of AMI (chest discomfort, diaphoresis, shortness of breath, nausea, and lightheadedness). These AMI symptom clusters must be communicated clearly to the public in a way that will assist them in assessing their symptoms more efficiently and will guide their treatment-seeking behavior. Symptom clusters for AMI must also be communicated to the professional community in a way that will facilitate assessment and rapid intervention for AMI