Rapid evolution in the wild: changes in body size, life-history traits, and behavior in hunted populations of the Japanese mamushi snake.

Rapid evolution caused by human exploitation of wildlife is not usually addressed in studies of the impacts of such exploitation despite its direct relevance to population persistence. Japanese mamushi (Gloydius blomhoffii), an endemic venomous snake of the Japanese archipelago, has been heavily hunted by humans, and many populations appear to be declining or are already extirpated. We compared local populations that have been hunted regularly with populations that have not been hunted. Mamushi in hunted populations were smaller, had fewer vertebrae, produced more and smaller offspring, had increased reproductive effort among smaller females, and in nature fled at greater distances from an approaching human and were less defensive than mamushi in unhunted populations, as predicted from life-history theory. Heritability estimates for body size, number of vertebrae, and antipredator behavior were statistically significant, and neonates from hunted sites showed the same distribution of altered characters (compared with those from unhunted sites) as adults. Thus, distribution of the divergent trait between hunted and unhunted sites appeared in part to be genetically based, which suggests rapid evolution to human predation pressures. Trait distributions in hunted populations probably deviate from naturally (as opposed to anthropogenically) selected optima and, therefore, may have long-term negative repercussions on population persistence. Because rapid evolution affects a suite of parameters that characterize exploited populations, accurate understanding of the impacts of exploitation and effective resource management and conservation can only be achieved if evolutionary consequences are considered explicitly.

Conflict of interest or ideological divide: the need for ongoing collaboration between physicians and industry.

Continued collaboration between the health profession and industry is essential for future innovation and for fighting disease and illness well into the 21st century. Evidence that suggests conflicts of interest have a negative effect on patient care or the total cost of health care is lacking. Many arguments put forth to address this issue include strictly limiting or severing ties with industry. Research takes place in university, government, and pharmaceutical laboratories, but only industry translates research into drug therapy. While both parties have a shared goal of optimizing health outcomes, industry critics conveniently invoke 'conflict of interest' to express their opinion about the need to more strictly regulate physician/industry interactions. Retreat from industry by academic institutions and working in isolation are simply not strategic options and other points of view must be expressed to help avoid the 'triumph of emotion over fact'.

Injury severity and comorbidities alone do not predict futility of care after geriatric trauma.

BACKGROUND: When counseling surrogates of massively injured elderly trauma patients, the prognostic information they desire is rarely evidence based. OBJECTIVE: We sought to objectively predict futility of care in the massively injured elderly trauma patient using easily available parameters: age, Injury Severity Score (ISS), and preinjury comorbidities. METHODS: Two cohorts (70-79 years and ≥80 years) were constructed from The National Trauma Data Bank (NTDB) for years 2007-2011. Comorbidities were tabulated for each patient. Mortality rates at every ISS score were tabulated for subjects with 0, 1, or ≥2 comorbidities. Futility was defined a priori as an in-hospital mortality rate of ≥95% in a cell with ≥5 subjects. RESULTS: A total of 570,442 subjects were identified (age 70-79 years, n=217,384; age ≥80 years, n=352,608). Overall mortality was 5.3% for ages 70-79 and 6.6% for ≥80 years. No individual ISS score was found to have a mortality rate of ≥95% for any number of comorbidities in either age cohort. The highest mortality rate seen in any cell was for an ISS of 66 in the ≥80 year-old cohort with no listed comorbidities (93.3%). When upper extremes of ISS were aggregated into deciles, mortality for both cohorts across all number of comorbidities was 45.5%-60.9% for ISS 40-49, 56.6%-81.4% for ISS 50-59, and 73.9%-93.3% for ISS ≥60. CONCLUSIONS: ISS and preinjury comorbidities alone cannot be used to predict futility in massively injured elderly trauma patients. Future attempts to predict futility in these age groups may benefit from incorporating measures of physiologic distress.

Consequences of unlocking the cardiac myosin molecule in human myocarditis and cardiomyopathies.

Myocarditis, often initiated by viral infection, may progress to autoimmune inflammatory heart disease, dilated cardiomyopathy and heart failure. Although cardiac myosin is a dominant autoantigen in animal models of myocarditis and is released from the heart during viral myocarditis, the characterization, role and significance of anti-cardiac myosin autoantibodies is poorly defined. In our study, we define the human cardiac myosin epitopes in human myocarditis and cardiomyopathies and establish a mechanism to explain how anti-cardiac myosin autoantibodies may contribute to heart disease. We show that autoantibodies to cardiac myosin in sera from myocarditis and dilated cardiomyopathies in humans targeted primarily epitopes in the S2 hinge region of cardiac myosin. In addition, anti-cardiac myosin antibodies in sera or purified IgG from myocarditis and cardiomyopathy targeted the beta-adrenergic receptor and induced antibody-mediated cAMP-dependent protein kinase A (PKA) cell signaling activity in heart cells. Antibody-mediated PKA activity in sera was abrogated by absorption with anti-human IgG. Antibody-mediated cell signaling of PKA was blocked by antigen-specific inhibition by human cardiac myosin or the beta-adrenergic receptor but not the alpha adrenergic receptor or bovine serum albumin. Propranolol, a beta blocker and inhibitor of the beta-adrenergic receptor pathway also blocked the antibody-mediated signaling of the beta-adrenergic receptor and PKA. The data suggest that IgG antibody against human cardiac myosin reacts with the beta-adrenergic receptor and triggers PKA signaling in heart cells. In summary, we have identified a new class of crossreactive autoantibodies against human cardiac myosin and the beta-adrenergic receptor in the heart. In addition, we have defined disease specific peptide epitopes in the human cardiac myosin rod S2 region in human myocarditis and cardiomyopathy as well as a mechanistic role of autoantibody in the pathogenesis of disease.