Bonsai Trees in Your Head: How the Pavlovian System Sculpts Goal-Directed Choices by Pruning Decision Trees

When planning a series of actions, it is usually infeasible to consider all potential future sequences; instead, one must prune the decision tree. Provably optimal pruning is, however, still computationally ruinous and the specific approximations humans employ remain unknown. We designed a new sequential reinforcement-based task and showed that human subjects adopted a simple pruning strategy: during mental evaluation of a sequence of choices, they curtailed any further evaluation of a sequence as soon as they encountered a large loss. This pruning strategy was Pavlovian: it was reflexively evoked by large losses and persisted even when overwhelmingly counterproductive. It was also evident above and beyond loss aversion. We found that the tendency towards Pavlovian pruning was selectively predicted by the degree to which subjects exhibited sub-clinical mood disturbance, in accordance with theories that ascribe Pavlovian behavioural inhibition, via serotonin, a role in mood disorders. We conclude that Pavlovian behavioural inhibition shapes highly flexible, goal-directed choices in a manner that may be important for theories of decision-making in mood disorders

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Transforming Pinus pinaster forest to recreation site: Preliminary effects on LAI, some forest floor, and soil properties

This study investigates the effects of forest transformation into recreation site. A fragment of a Pinus pinaster plantation forest was transferred to a recreation site in the city of BartIn located close to the Black Sea coast of northwestern Turkey. During the transformation, some of the trees were selectively removed from the forest to generate more open spaces for the recreationists. As a result, Leaf Area Index (LAI) decreased by 0.20 (about 11 %). Additionally, roads and pathways were introduced into the site together with some recreational equipment sealing parts of the soil surface. Consequently, forest environment was altered with a semi-natural landscape within the recreation site. The purpose of this study is to assess the effects of forest transformation into recreation site particularly in terms of the LAI parameter, forest floor, and soil properties. Preliminary monitoring results indicate that forest floor biomass is reduced by 26 % in the recreation site compared to the control site. Soil temperature is increased by 15 % in the recreation site where selective removal of trees expanded the gaps allowing more light transmission. On the other hand, the soil bulk density which is an indicator of soil compaction is unexpectedly slightly lower in the recreation site. Organic carbon (Corg) and total nitrogen (Ntotal) together with the other physical and chemical parameter values indicate that forest floor and soil have not been exposed to much disturbance. However, subsequent removal of trees that would threaten the vegetation, forest floor, and soil should not be allowed. The activities of the recreationists are to be concentrated on the paved spaces rather than soil surfaces. Furthermore, long-term monitoring and management is necessary for both the observation and conservation of the site. © 2013 Springer Science+Business Media

Notonuphar antarctica, an extinct water lily (Nymphaeales) from the Eocene of Antarctica

A new genus and species, Notonuphar antarctica, is described from the Eocene of Seymour (Marambio) Island, the Antarctic Peninsula and assigned to the Nymphaeales based on well-preserved seeds. This is the first record of a water lily from Antarctica and the first record of a Gondwanan plant with close link to the genus Nuphar (Nymphaeaceae), which is restricted today to the Northern Hemisphere. Critical features for systematic placement of Notonuphar are the presence of a germination cap with closely spaced hilar scar and micropyle, anatropous, bitegmic and exotestal seed organization, exotesta composed of one cell layer of high sclerenchymatic palisade-shape cells, mesotesta of smaller, low parenchymatic cells, a few cell layers deep, and a thin tegmen. The seeds of Notonuphar are particularly similar to seeds of extant and fossil Nuphar in the straight, unfolded anticlinal wall of the exotestal cells and the presence of a narrow zone of exotestal tissue between hilum and micropyle. Other seed features including the very tall exotestal cells and strongly thickened cell walls of exotesta also link Notonuphar to Brasenia and related fossil taxa (Cabombaceae). This character mosaic observed in Notonuphar corroborates the transitional position of Nuphar between Cabombaceae and Nymphaeaceae. Notonuphar is the only member of Nymphaeales recorded from Antarctica and so far the only fossil seeds of Nymphaeales known from the Southern Hemisphere. The discovery of this extinct Gondwanan taxon with features suggesting close relationship with extant Northern Hemisphere genus Nuphar is a further evidence for the relictual nature of the extant group.Other funding from:Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET Grant PIP 0462 to MAR.), the Argentine National Agency for Promotion of Science and Technology (ANPCyT Grant PICTO-2010–0093 to MAR) and the Paul Scherrer Institute https://www.psi.ch/useroffice/useroffice (projects 20130185, 20141047, 2016140)</p