A One Health Approach to Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease in humans and results in significant morbidity and mortality. Research over the past 25 years has contributed enormous insight into this inherited disease particularly in the areas of genetics, molecular mechanisms, and pathophysiology. Our understanding continues to be limited by the heterogeneity of clinical presentations with various genetic mutations associated with HCM. Transgenic mouse models have been utilized especially studying the genotypic and phenotypic interactions. However, mice possess intrinsic cardiac and hemodynamic differences compared to humans and have limitations preventing their direct translation. Other animal models of HCM have been studied or generated in part to overcome these limitations. HCM in cats shows strikingly similar molecular, histopathological, and genetic similarities to human HCM, and offers an important translational opportunity for the study of this disease. Recently, inherited left ventricular hypertrophy in rhesus macaques was identified and collaborative investigations have been conducted to begin to develop a non-human primate HCM model. These naturally-occurring large-animal models may aid in advancing our understanding of HCM and developing novel therapeutic approaches to this disease. This review will highlight the features of HCM in humans and the relevant available and developing animal models of this condition

Sulfur-bound biomarkers of a Monterey shale and a Greenland lake sediment

Seeking to reconstruct the biogeochemical processes that produced organic sulfur compounds in two unique depositional environments, we used the nickel boride desulfurization reaction to release hydrocarbons from sulfur-bound macromolecules not otherwise amenable to chromatographic analysis. We desulfurized two geochemical extracts: one sample is a Monterey shale of late Miocene age, and the other sample is a surface sediment from the Greenland lake Brayasø. Both samples contained organic sulfur compounds, but the Monterey shale was biologically and thermally modified after deposition. A comparison of the free and sulfur-bound hydrocarbons from each sample revealed a precursor-product relationship between tocopherol and pristane, for Monterey. Greenland’s composition may indicate that photochemical sulfurization occurs in the Brayasø oxic zone. We found that sulfurization may proceed at different rates for different compound families; for example, we did not see any sulfurized alkenones in Brayasø, but we found an abundance of sulfurized isoprenoids. Greenland’s relatively high overall desulfurization yield suggests that sulfurization in Brayasø occurs in under 40 years. Our Greenland findings suggest that photochemical sulfurization may be more widespread than previously thought, and that sulfurization might not interfere with alkenone paleotemperature reconstructions

The Impact of Uncertain Intellectual Property Rights on the Market For Ideas: Evidence From Patent Grant Delays

This paper considers the impact of the intellectual property (IP) system on the timing of cooperation/licensing by start-up technology entrepreneurs. If the market for technology licenses is efficient, the timing of licensing is independent of whether IP has already been granted. In contrast, the need to disclosure complementary (yet unprotected) knowledge, asymmetric information, or search costs may retard efficient technology transfer. In these cases, reductions in uncertainty surrounding the scope and extent of IP rights may facilitate trade in the market for ideas. We employ a dataset combining information about cooperative licensing and the timing of patent allowances (the administrative event when patent rights are clarified). While pre-allowance licensing does occur, the hazard rate for achieving a cooperative licensing agreement significantly increases after patent allowance. Moreover, the impact of the patent system depends on the strategic and institutional environment in which firms operate. Patent allowance seems to play a particularly important role for technologies with longer technology lifecycles or that lack alternative mechanisms such as copyright, reputation, or brokers. The findings suggest that imperfections in the market for ideas may be important, and that formal IP rights may facilitate gains from technological trade.

When Does Start-Up Innovation Spur the Gale of Creative Destruction?

This paper is motivated by the substantial differences in start-up commercialization strategies observed across different high-technology sectors. Specifically, we evaluate the conditions under which start-up innovators earn their returns on innovation through product market competition with more established firms (such as in many areas of the electronics industry) as opposed to cooperation with these incumbents (either through licensing, strategic alliances or outright acquisition as observed in the pharmaceutical industry). While the former strategy challenges incumbent market power, the latter strategy tends to reinforce current market structure. Though the benefits of cooperation include forestalling the costs of competition in the product market and avoiding duplicative investment in sunk assets, imperfections in the market for ideas' may lead to competitive behavior in the product market. Specifically, if the transaction costs of bargaining are high or incumbents are likely to expropriate ideas from start-up innovators, then product market competition is more likely. We test these ideas using a novel dataset of the commercialization strategies of over 100 start-up innovators. Our principal robust findings are that the probability of cooperation is increasing in the innovator's control over intellectual property rights, association with venture capitalists (which reduce their transactional bargaining costs), and in the relative cost of control of specialized complementary assets. Our conclusion is that the propensity for pro-competitive benefits from start-up innovators reflects an earlier market failure, in the market for ideas.'

Endogenous Appropriability

Innovation’s private value is typically less than its social value, so to encourage innova- tion, researchers in economics and strategy have focused on how innovators can appropri- ate value across different economic, institu- tional, and strategic environments ( Teece 1986; Gans and Stern 2003 ) . For sta rt-ups without pre-existing assets such as manufacturing capa- bilities or brand reputation, researchers have identified appropriability through formal intel- lectual property protection ( which we will refer to as a “control” approach ) and first-mover com- petitive advantage ( which we will refer to as an “execution” approach ) as distinct paths. Most research has taken a start-up’s appro- priability regime as exogenous, i.e., environ- mentally determined ( e.g., control-orientation in biotechnology, and execution-orientation in Internet software ) . This paper develops a simple model highlighting the interplay between con- trol and execution as alternative routes to appro- priability. Whereas a control strategy allows an innovator to forestall imitation once established, control itself takes time, and so can delay market entry. In contrast, an execution strategy is pre- mised on taking advantage of the benefits aris- ing from rapid market entry such as customer learning, reputational advantages, or coordina- tion on a standard. Does the start-up shield itself from competition through investing in entry barriers or does it invest in dynamic capabilities allowing it to “get ahead, stay ahead”? We derive two main results. First, the choices of control and execution are strategic substi- tutes. Notably, when the ability to learn from early customer feedback in the marketplace is sufficiently high, an entrepreneur might choose not to invest in intellectual property protection even if such protection is costless and effective. Second, the choice between control and execu- tion interacts with other key strategic choices such as whether to pursue a narrow or broad customer segment, or whether to commercialize a “minimal viable product” versus a more robust version. Innovation appropriability depends not only on the instruments available to an innova- tor, but on how those instruments interact with each other as part of the firm’s ( endogenous ) entrepreneurial strategy (see Ching, Gans, and Stern 2016; Gans, Stern, and Wu 2016 )

Feline Hypertrophic Cardiomyopathy: A Spontaneous Large Animal Model of Human HCM.

Hypertrophic cardiomyopathy (HCM) is a common disease in pet cats, affecting 10-15% of the pet cat population. The similarity to human HCM, the rapid progression of disease, and the defined and readily determined endpoints of feline HCM make it an excellent natural model that is genotypically and phenotypically similar to human HCM. The Maine Coon and Ragdoll cats are particularly valuable models of HCM because of myosin binding protein-C mutations and even higher disease incidence compared to the overall feline population. The cat overcomes many of the limitations of rodent HCM models, and can provide enhanced translation of information from in vitro and induced small animal models to human clinical trials. Physicians and veterinarians working together in a collaborative and interdisciplinary approach can accelerate the discovery of more effective treatments for this and other cardiovascular diseases affecting human and veterinary patients

Cats with thermal burn injuries from California wildfires show echocardiographic evidence of myocardial thickening and intracardiac thrombi.

Recent increases in the prevalence and severity of wildfires in some regions have resulted in an increased frequency of veterinary burn patients. Few studies exist regarding diagnostics and management of burn wounds in veterinary patients and current knowledge is extrapolated from human literature and research models. Post-burn cardiac injury is a common finding and predictor of mortality in human patients and echocardiography is an important tool in monitoring response to therapy and predicting outcome. We describe the notable findings from cats naturally exposed to California wildfires in 2017 and 2018. Domestic cats (n = 51) sustaining burn injuries from the Tubbs (2017) and Camp (2018) wildfires were prospectively enrolled and serial echocardiograms and cardiac troponin I evaluations were performed. Echocardiograms of affected cats revealed a high prevalence of myocardial thickening (18/51) and spontaneous echocardiographic contrast and thrombi formation (16/51). Forty-two cats survived to discharge and 6 died or were euthanized due to a possible cardiac cause. For the first time, we describe cardiovascular and coagulation effects of thermal burn and smoke inhalation in cats. Further studies in veterinary burn victims are warranted and serve as a translational research opportunity for uncovering novel disease mechanisms and therapies

Echocardiographic evaluation of velocity ratio, velocity time integral ratio, and pulmonary valve area in dogs with pulmonary valve stenosis.

BackgroundVelocity ratio, velocity time integral (VTI) ratio, and pulmonary valve area indexed to body surface area (iPVA) are methods of assessment of pulmonary valve stenosis (PS) severity that are less dependent on blood flow. Studies evaluating these methods are limited.ObjectivesTo determine the effects of butorphanol, atenolol, and balloon valvuloplasty (BV) on velocity ratio, VTI ratio, iPVA, mean PG, and max PG.AnimalsTwenty-seven dogs with PS (max PG >50 mm Hg).MethodsProspective study. All dogs underwent an echocardiogram at baseline, 5-minutes after administration of butorphanol (0.2-0.25 mg/kg IV), and 2-to-4 weeks after atenolol (1-1.5 mg/kg q12h). Twenty-one of these were evaluated 24-hours after BV.ResultsThere were no significant differences (P > .05) amongst any of the methods of assessment of PS severity after butorphanol. After atenolol, mean (SD) of mean (57.0 [21.0] mm Hg) and max PG (93.1 [33.8] mm Hg) were significantly decreased (P ≤ .047) compared with baseline (65.2 [26.2] mm Hg and 108 [44.4] mm Hg, respectively). After atenolol, there were no significant (P ≥ .12) differences in velocity ratio (0.29 [0.09]), VTI ratio (0.18 [0.05]), or iPVA (0.43 [0.16] cm2 /m2 ) compared with baseline (0.30 [0.09], 0.19 [0.09], 0.44 [0.17] cm2 /m2 , respectively).Conclusions and clinical importanceAtenolol might reduce mean and max PG but does not alter less flow-dependent methods of assessment of PS severity (velocity ratio, VTI ratio, and iPVA) in dogs with PS. Results support an integrative approach to assessment of PS severity that includes less flow-dependent methods, particularly in states of altered flow or right ventricular function