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Rising sea levels necessitate careful consideration of different forms of coastal protection but cost-benefit analysis is limited when important non-market social costs have not been measured. Seawalls protect individual properties but can potentially impose negative externalities on neighboring properties via accelerated beach loss. We conduct a hedonic valuation of seawalls in two coastal California counties: San Diego and Santa Cruz. We find no strong evidence to suggest that the presence of a seawall is positively correlated with the value of the home protected. However, we find that seawalls are strongly negatively correlated with the value of neighboring properties in Santa Cruz but not in San Diego county, suggesting that the effect of seawalls depend on certain geographical attributes. Our results are robust to accounting for the public-good nature of locational attributes and the potential spatial dependence of housing prices. Simulation reveals that doubling the extent of seawalls in San Diego and Santa Cruz could reduce property tax revenues by $7 million and $54 million, respectively.

It is commonly agreed that marine conservation should expand considerably around the world. However, most countries have not yet implemented large-scale no-take Marine Protected Areas (MPAs). When a country closes a large fraction of its waters to fishing, it stands to lose a considerable level of fishery revenue. Although biodiversity and spillover fishing benefits may far exceed these losses, benefits from large-scale MPAs typically accrue to other countries or to the high seas. Here, to overcome this dilemma, we simulate and test an international fisheries management scheme with transferable fishing rights that incentivizes, rather than hinders, large-scale marine conservation. By combining a bioeconomic model of cross-country trading of fishing rights with vessel-level tracking data before and after a large-scale conservation action is implemented, we show that transferable fishing rights and a biomass-based allocation rule are pivotal to incentivize conservation under this market-based setting. Our work focuses on the Vessel Day Scheme (VDS)—an environmental market that is employed by the Parties to the Nauru Agreement (a group of nine Pacific Island nations) to manage their tuna fisheries—and areas in which large-scale conservation interventions have taken place. Overall, these results provide a template for how to incentivize countries to engage in large-scale marine conservation within a market-based setting. An international arrangement of transferable fishing rights and biomass-based allocation can incentivize establishing Marine Protected Areas while promoting the economy.

Evaluation of the economic impacts of marine protected areas is hampered by the fact that it is impossible to observe what would have happened if the protected area had never been closed to fishing (the counterfactual). Catch reports and vessel tracks are used to perform an analysis of the potential negative economic impacts of establishing the Northeast Canyons and Seamounts Marine National Monument (located off the east coast of the United States of America) on three commercially important fisheries that were identified as having potential to be harmed. I conclude that there was little to no negative impact on any of the fisheries. I also test for, but find no evidence of, a Blue Paradox effect. Due to political factors largely unrelated to fisheries status, the protected area was reopened to commercial fishing on June 5th, 2020. I use this event, which was reversed sixteen months later, to test whether there were any economic benefits from reopening. I do not observe an increase in catch, a reduction in distance traveled, or an increase in relative fishing effort inside the protected area (compared to historical trends), consistent with the post-closure findings.

The ongoing emission of greenhouse gases (GHGs) is triggering changes in many climate hazards that can impact humanity. We found traceable evidence for 467 pathways by which human health, water, food, economy, infrastructure and security have been recently impacted by climate hazards such as warming, heatwaves, precipitation, drought, floods, fires, storms, sea-level rise and changes in natural land cover and ocean chemistry. By 2100, the world’s population will be exposed concurrently to the equivalent of the largest magnitude in one of these hazards if emmisions are aggressively reduced, or three if they are not, with some tropical coastal areas facing up to six simultaneous hazards. These findings highlight the fact that GHG emissions pose a broad threat to humanity by intensifying multiple hazards to which humanity is vulnerable.

Perhaps the greatest challenge facing global fisheries is that recovery often requires substantial short-term reductions in fishing effort, catches and profits. These costs can be onerous and are borne in the present; thus, many countries are unwilling to undertake such socially and politically unpopular actions. We argue that many nations can recover their fisheries while avoiding these short-term costs by sharply addressing illegal, unreported and unregulated (IUU) fishing. This can spur fishery recovery, often at little or no cost to local economies or food provision. Indonesia recently implemented aggressive policies to curtail the high levels of IUU fishing it experiences from foreign-flagged vessels. We show that Indonesia’s policies have reduced total fishing effort by at least 25%, illustrating with empirical evidence the possibility of achieving fishery reform without short-term losses to the local fishery economy. Compared with using typical management reforms that would require a 15% reduction in catch and 16% reduction in profit, the approach of curtailing IUU has the potential to generate a 14% increase in catch and a 12% increase in profit. Applying this model globally, we find that addressing IUU fishing could facilitate similar rapid, long-lasting fisheries gains in many regions of the world. Analysis of Indonesia’s recent push to aggressively police illegal, unreported and unregulated fishing demonstrates a cost-effective way to improve fisheries recovery while limiting the reduction of legal catch (and the subsequent impact on food supply and profit) that could be applied to other regions.

There is conflicting evidence about whether abundant resources are indeed a blessing or a curse. We make use of specially designed economic experiments to investigate how resource abundance affects cooperation in the absence or presence of regulatory institutions. We observe that in the absence of regulatory institutions, there is less cooperation in groups with access to large resource pools than in groups with access to small resource pools. However, if regulatory institutions are present, we show that there is more cooperation in groups with access to large resource pools than in groups with access to small resource pools. Our findings also reveal that resource users are more willing to regulate access to abundant than to small resource pools. These findings provide causal evidence for the “paradox of plenty” and identify the causes for the pitfalls and potentials of resource wealth.

Restoration of critical sized defects of the mandible still poses a major problem in the field of Oral and Maxillofacial Surgery. The current gold standard of treatment relies on the use of autologous grafts and therefore, has associated disadvantages such as donor site morbidity and insufficient bone for prosthetic rehabilitation. Recent advances in the fields of bone tissue engineering and distraction osteogenesis provide an alternative treatment modality to restore the aforementioned critical sized defects. These alternative modalities offer patients and clinicians multiple advantages such as decreased morbidity and increased volume of bone for prosthetic restoration. The aim of this review was to evaluate the bone regeneration capacity of bone tissue engineering and distraction osteogenesis in preclinical in vivo animal models against the current gold standard.

Author(s): Pardinas, Antonio F; Holmans, Peter; Pocklington, Andrew J; Escott-Price, Valentina; Ripke, Stephan; Carrera, Noa; Legge, Sophie E; Bishop, Sophie; Cameron, Darren; Hamshere, Marian L; Han, Jun; Hubbard, Leon; Lynham, Amy; Mantripragada, Kiran; Rees, Elliott; MacCabe, James H; McCarroll, Steven A; Baune, Bernhard T; Breen, Gerome; Byrne, Enda M; Dannlowski, Udo; Eley, Thalia C; Hayward, Caroline; Martin, Nicholas G; McIntosh, Andrew M; Plomin, Robert; Porteous, David J; Wray, Naomi R; Caballero, Armando; Geschwind, Daniel H; Huckins, Laura M; Ruderfer, Douglas M; Santiago, Enrique; Sklar, Pamela; Stahl, Eli A; Won, Hyejung; Agerbo, Esben; Als, Thomas D; Andreassen, Ole A; Baekvad-Hansen, Marie; Mortensen, Preben Bo; Pedersen, Carsten Bocker; Borglum, Anders D; Bybjerg-Grauholm, Jonas; Djurovic, Srdjan; Durmishi, Naser; Pedersen, Marianne Giortz; Golimbet, Vera; Grove, Jakob; Hougaard, David M; Mattheisen, Manuel; Molden, Espen; Mors, Ole; Nordentoft, Merete; Pejovic-Milovancevic, Milica; Sigurdsson, Engilbert; Silagadze, Teimuraz; Hansen, Christine Soholm; Stefansson, Kari; Stefansson, Hreinn; Steinberg, Stacy; Tosato, Sarah; Werge, Thomas; GERAD1 Consortium; CRESTAR Consortium; Collier, David A; Rujescu, Dan; Kirov, George; Owen, Michael J; O'Donovan, Michael C; Walters, James TR | Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The beta-blocker (-)-pindolol produces intrinsic sympathomimetic activity manifested clinically by cardiostimulation, but the beta-adrenoceptor subtype, which mediates these effects, is unknown. Recent work indicates the existence of a (-)-propranolol-resistant site of the cardiac beta(1)-adrenoceptor and we propose that it mediates the cardiostimulation evoked by (-)-pindolol. We compared the interaction of (-)-pindolol both with human atrial myocardium and with recombinant beta(1)-adrenoceptors. The effects of (-)-pindolol on paced human atrial trabeculae were studied in the presence of 3-isobutyl-1-methylxanthine (IBMX; 20 microM). (-)-Pindolol caused small negative and positive inotropic effects at nanomolar and micromolar concentrations respectively, which were unaffected by N(G)-monomethyl-L-arginine (L-NMMA, 10 microM), inconsistent with an involvement of nitric oxide. (-)-Pindolol, in the presence of (-)-propranolol, increased atrial contractile force and cAMP through recombinant beta(1)-adrenoceptors with identical potency (-logEC(50)M=6.5). The positive inotropic effects of (-)-pindolol were resistant to blockade by L-748,337 (100 nM), a beta(3)-adrenoceptor antagonist. (-)-CGP12177, known to act through the (-)-propranolol-resistant site of the beta(1)-adrenoceptor, also increased with similar potency atrial contractile force (-logEC(50)M=7.6) and cAMP at recombinant beta(1)-adrenoceptors (-logEC(50)M=7.7). (-)-Pindolol blocked the effects of (-)-CGP12177 in human atrium and recombinant beta(1)-adrenoceptors with similar equilibrium dissociation constants (pK(B)=6.5 and 6.3). Thus, stimulant potency and blocking potency of (-)-pindolol against (-)-CGP12177 agree. In contrast, (-)-pindolol was 200-400 times more effective at blocking the effects of a catecholamine than the effects of (-)-CGP12177 in both human atrium (pK(B)=9.1) and at recombinant beta(1)-adrenoceptors (pK(B)=8.6). We conclude that the cardiostimulant effects of (-)-pindolol in human atrial myocardium are mediated through a (-)-propranolol-resistant site of the beta(1)-adrenoceptor with low affinity for (-)-pindolol. In contrast, (-)-pindolol blocks the effects of catecholamines through a high-affinity site of the beta(1)-adrenoceptor. beta(3)-Adrenoceptors are not involved in the atrial effects of (-)-pindolol.

In this study outputs from four current General Circulation Models (GCMs) were used to project forest fire danger levels in Canada and Russia under a warmer climate. Temperature and precipitation anomalies between 1 × CO2 and 2 × CO2 runs were combined with baseline observed weather data for both countries for the 1980–1989 period. Forecast seasonal fire weather severity was similar for the four GCMs, indicating large increases in the areal extent of extreme fire danger in both countries under a 2 × CO2 climate scenario. A monthly analysis, using the Canadian GCM, showed an earlier start to the fire season, and significant increases in the area experiencing high to extreme fire danger in both Canada and Russia, particularly during June and July. Climate change as forecast has serious implications for forest fire management in both countries. More severe fire weather, coupled with continued economic constraints and downsizing, mean more fire activity in the future is a virtual certainty. The likely response will be a restructuring of protection priorities to support more intensive protection of smaller, high-value areas, and a return to natural fire regimes over larger areas of both Canada and Russia, with resultant significant impacts on the carbon budget.

We have reported that chronic treatment of patients with beta 1-adrenoceptor blockers sensitises isolated atrial preparations to adrenaline, noradrenaline and 5-Ht. We have now examined the effect of chronic treatment with beta-adrenoceptor blockers on responses to histamine of human right atrial appendages. We compared the effects of histamine on contractile force, cyclic AMP and cyclic GMP levels as well as cyclic AMP-dependent protein kinase (PKA) activity and explored the arrhythmogenic effects of histamine in preparations obtained from patients chronically treated or not treated with beta-adrenoceptor blockers. Histamine increased contractile force in paced preparations; the effects were blocked by the H2 receptor antagonist famotidine (0.1-30 mumol/l). The maximum inotropic response to histamine was doubled and the inotropic potency of histamine 0.4 log units greater in atria from beta-adrenoceptor blocker-treated compared to non beta-adrenoceptor blocker-treated patients. Histamine elicited frequency-dependent arrhythmias that were blocked by famotidine (30 mumol/l) but not by mepyramine (1 mumol/l). The incidence of arrhythmias was higher in atria from beta-adrenoceptor blocker-treated compared to untreated patients. Histamine increased both cyclic AMP and cyclic GMP levels, as well as PKA activity, significantly more in atria from beta-adrenoceptor blocker-treated compared to those from untreated patients. Mepyramine 1 mumol/l prevented the histamine-evoked increase in cyclic GMP levels, reduced the inotropic hyperresponsiveness and abolished the hyperresponsiveness in cyclic AMP levels and PKA activity observed in patients chronically treated with beta blockers. Sodium nitroprusside 10 mumol/l caused smaller increase of cyclic GMP levels than histamine and restored the contracile force depressed by mepyramine to its original level in atria from beta-adrenoceptor blocker-treated patients. The evidence is consistent with sensitisation of both the histamine H1 and histamine H2 receptor systems by chronic beta 1-adrenoceptor blockade. H1 receptor-mediated increases in cyclic GMP, enhanced through an as yet unknown mechanism by chronic beta 1-adrenoceptor blockade, may inhibit phosphodiesterase 3 activity, thereby causing enhanced histamine-evoked increases in cyclic AMP levels and PKA activity, and accounting partially for the increased inotropic responses to histamine through H2 receptors.

Evidence from ventricular preparations of cat, sheep, rat and dog suggests that both beta 1-adrenoceptors (beta 1AR) and beta 2-adrenoceptors (beta 2AR) mediate positive inotropic effects but that only beta 1AR do it through activation of a cAMP pathway. On the other hand, our evidence has shown that both beta 1AR and beta 2AR hasten relaxation of isolated human myocardium consistent with a common cAMP pathway. We have now investigated in the isolated human right atrial appendage, a tissue whose beta-AR comprise around 2/3 of beta 1AR and 1/3 of beta 2AR, whether or not beta 2AR-mediated effects occur via activation of a cAMP pathway. We carried out experiments on atria obtained from patients without advanced heart failure undergoing open heart surgery. To activate beta 2AR, we used the beta 2AR-selective ligand zinterol. Experiments were carried out on paced atrial strips (1 Hz) and tissue homogenates and membrane particles. Zinterol caused positive inotropic and lusitropic (i.e. reduction of t1/2 of relaxation) effects with EC50 values of 3 and 2 nM, respectively. The zinterol-evoked effects were unaffected by the beta 1AR-selective antagonist CGP 20712A (300 nM) but blocked surmountably by the beta 2AR-selective antagonist ICI 118551 (50 nM) which reduced both EC50 values to 1 microM. Zinterol stimulated adenylyl cyclase activity with an EC50 of 30 nM and intrinsic activity of 0.75 with respect to (-)-isoprenaline (600 microM); the effects were resistant to blockade by CGP 20712A (300 nM) but antagonised surmountably by ICI 118551 (50 nM). Zinterol bound to membrane beta AR labelled with (-)-[125I] cyanopindolol with higher affinity for beta 2AR than for beta 1AR; the binding to beta 2AR but not to beta 1AR was reduced by GTP gamma S (10 microM). In the presence of CGP 20712A (300 nM) (-)-isoprenaline (400 microM) (to activate both beta 1AR and beta 2AR maximally) and zinterol (10 microM) increased contractile force 3.4-fold and 2.5-fold respectively and reduced relaxation t1/2 by 32% and 18% respectively. These effects of (-)-isoprenaline and zinterol were associated (5 min incubation) with phosphorylation (pmol P/mg supernatant protein) of troponin I and C-protein to values of 8.4 +/- 2.0 vs 12.4 +/- 2.3 and 10.1 +/- 2.5 vs 8.6 +/- 1.6 respectively. (-)-Isoprenaline and zinterol also caused phosphorylation of phospholamban (1.8 +/- 0.3 vs 0.4 +/- 0.1 pmol P/mg respectively) specifically at serine residues. We conclude that in human atrial myocardium activation of both beta 1AR and beta 2AR leads to cAMP-dependent phosphorylation of proteins involved in augmenting both contractility and relaxation.

Serotonin (5-hydroxytryptamine, 5-HT) increases contractile force and elicits arrhythmias through 5-HT(4) receptors in porcine and human atrium, but its ventricular effects are unknown. We now report functional 5-HT(4) receptors in porcine and human ventricle. 5-HT(4) mRNA levels were determined in porcine and human ventricles and contractility studied in ventricular trabeculae. Cyclic AMP-dependent protein kinase (PKA) activity was measured in porcine ventricle. Porcine and human ventricles expressed 5-HT(4) receptor mRNA. Ventricular 5-HT(4(b)) mRNA was increased by four times in 20 failing human hearts compared with five donor hearts. 5-HT increased contractile force maximally by 16% (EC(50)=890 nM) and PKA activity by 20% of the effects of (-)-isoproterenol (200 microM) in ventricular trabeculae from new-born piglets in the presence of the phosphodiesterase-inhibitor 3-isobutyl-1-methylxanthine. In ventricular trabeculae from adult pigs (3-isobutyl-1-methylxanthine present) 5-HT increased force by 32% (EC(50)=60 nM) and PKA activity by 39% of (-)-isoproterenol. In right and left ventricular trabeculae from failing hearts, exposed to modified Krebs solution, 5-HT produced variable increases in contractile force in right ventricular trabeculae from 4 out of 6 hearts and in left ventricular trabeculae from 3 out of 3 hearts- range 1-39% of (-)-isoproterenol, average 8%. In 11 left ventricular trabeculae from the failing hearts of four beta-blocker-treated patients, pre-exposed to a relaxant solution with 0.5 mM Ca(2+) and 1.2 mM Mg(2+) followed by a switch to 2.5 mM Ca(2+) and 1 mM Mg(2+), 5-HT (1-100 microM, 3-isobutyl-1-methylxanthine present) consistently increased contractile force and hastened relaxation by 46% and 25% of (-)-isoproterenol respectively. 5-HT caused arrhythmias in three trabeculae from 3 out of 11 patients. In the absence of phosphodiesterase inhibitor, 5-HT increased force in two trabeculae, but not in another six trabeculae from 4 patients. All 5-HT responses were blocked by 5-HT(4) receptor antagonists. We conclude that phosphodiesterase inhibition uncovers functional ventricular 5-HT(4) receptors, coupled to a PKA pathway, through which 5-HT enhances contractility, hastens relaxation and can potentially cause arrhythmias.