23 research outputs found
The Effect of Recurrent Floods on Genetic Composition of Marble Trout Populations
A changing global climate can threaten the diversity of species and ecosystems. We explore the consequences of catastrophic disturbances in determining the evolutionary and demographic histories of secluded marble trout populations in Slovenian streams subjected to weather extremes, in particular recurrent flash floods and debris flows causing massive mortalities. Using microsatellite data, a pattern of extreme genetic differentiation was found among populations (global FST of 0.716), which exceeds the highest values reported in freshwater fish. All locations showed low levels of genetic diversity as evidenced by low heterozygosities and a mean of only 2 alleles per locus, with few or no rare alleles. Many loci showed a discontinuous allele distribution, with missing alleles across the allele size range, suggestive of a population contraction. Accordingly, bottleneck episodes were inferred for all samples with a reduction in population size of 3–4 orders of magnitude. The reduced level of genetic diversity observed in all populations implies a strong impact of genetic drift, and suggests that along with limited gene flow, genetic differentiation might have been exacerbated by recurrent mortalities likely caused by flash flood and debris flows. Due to its low evolutionary potential the species might fail to cope with an intensification and altered frequency of flash flood events predicted to occur with climate change
Pharmacological validation of a novel nonhuman primate measure of thermal responsivity with utility for predicting analgesic effects
Joshua D Vardigan, Andrea K Houghton, Henry S Lange, Emily D Adarayan, Parul S Pall, Jeanine E Ballard, Darrell A Henze, Jason M Uslaner Merck Research Laboratories, West Point, PA, USA Introduction: The development of novel analgesics to treat acute or chronic pain has been a challenge due to a lack of translatable measurements. Preclinical end points with improved translatability are necessary to more accurately inform clinical testing paradigms, which may help guide selection of viable drug candidates. Methods: In this study, a nonhuman primate biomarker which is sensitive to standard analgesics at clinically relevant plasma concentrations, can differentiate analgesia from sedation and utilizes a protocol very similar to that which can be employed in human clinical studies is described. Specifically, acute heat stimuli were delivered to the volar forearm using a contact heat thermode in the same manner as the clinical setting. Results: Clinically efficacious exposures of morphine, fentanyl, and tramadol produced robust analgesic effects, whereas doses of diazepam that produce sedation had no effect. Conclusion: We propose that this assay has predictive utility that can help improve the probability of success for developing novel analgesics. Keywords: pain, opioid, translatable, monkey, thermode, noxious hea
Flooding and Emergency Room Visits for Gastrointestinal Illness in Massachusetts: A Case-Crossover Study
INTRODUCTION: Floods and other severe weather events are anticipated to increase as a result of global climate change. Floods can lead to outbreaks of gastroenteritis and other infectious diseases due to disruption of sewage and water infrastructure and impacts on sanitation and hygiene. Floods have also been indirectly associated with outbreaks through population displacement and crowding. METHODS: We conducted a case-crossover study to investigate the association between flooding and emergency room visits for gastrointestinal illness (ER-GI) in Massachusetts for the years 2003 through 2007. We obtained ER-GI visits from the State of Massachusetts and records of floods from the National Oceanic and Atmospheric Association's Storm Events Database. ER-GI visits were considered exposed if a flood occurred in the town of residence within three hazard periods of the visit: 0-4 days; 5-9 days; and 10-14 days. A time-stratified bi-directional design was used for control selection, matching on day of the week with two weeks lead or lag time from the ER-GI visit. Fixed effect logistic regression models were used to estimate the risk of ER-GI visits following the flood. RESULTS AND CONCLUSIONS: A total of 270,457 ER-GI visits and 129 floods occurred in Massachusetts over the study period. Across all counties, flooding was associated with an increased risk for ER-GI in the 0-4 day period after flooding (Odds Ratio: 1.08; 95% Confidence Interval: 1.03-1.12); but not the 5-9 days (Odds Ratio: 0.995; 95% Confidence Interval: 0.955-1.04) or the 10-14 days after (Odds Ratio: 0.966, 95% Confidence Interval: 0.927-1.01). Similar results were observed for different definitions of ER-GI. The effect differed across counties, suggesting local differences in the risk and impact of flooding. Statewide, across the study period, an estimated 7% of ER-GI visits in the 0-4 days after a flood event were attributable to flooding