EPS mid-career prize 2018: Inference within episodic memory reflects pattern completion

Recollection of episodic memories is a process of reconstruction where coherent events are inferred from subsets of remembered associations. Here, we investigated the formation of multielement events from sequential presentation of overlapping pairs of elements (people, places, and objects/animals), interleaved with pairs from other events. Retrievals of paired associations from a fully observed event (e.g., AB, BC, AC) were statistically dependent, indicating a process of pattern completion, but retrievals from a partially observed event (e.g., AB, BC, CD) were not. However, inference for unseen "indirect" associations (i.e., AC, BD or AD) from a partially observed event showed strong dependency with each other and with linking direct associations from that event. In addition, inference of indirect associations correlated with the product of performance on the linking direct associations across events (e.g., AC with ABxBC) but not on the non-linking association (e.g., AC with CD). These results were seen across three experiments, with greater differences in dependency between indirect and direct associations when they were separately tested, but similar results following single and repeated presentations of the direct associations. The results could be accounted for by a simple auto-associative network model of hippocampal memory function. Our findings suggest that pattern completion supports recollection of fully observed multielement events and the inference of indirect associations in partly observed multielement events, mediated via the directly observed linking associations (although the direct associations themselves were retrieved independently). Together with previous work, our results suggest that associative inference plays a key role in reconstructive episodic memory and does so through hippocampal pattern completion

The (im?)possibility of a biological substrate for mental disorders

ACHTERGROND Er bestaat een tegenstelling tussen de ‘medische’ kijk op een psychiatrische aandoening (als gegevenheid van de natuur in de zin van een biologisch substraat) en de constructivistische visie. DOEL Onderzoeken hoe de constructivistische positie zich verhoudt tot deze medische kijk op psychiatrische aandoeningen. METHODE Een beschouwing gebaseerd op een conceptuele analyse, met name van het boek The social construction of what? (1999) van de Canadese wetenschapsfilosoof Ian Hacking. RESULTATEN Er blijken verschillende objecten van constructivistische analyses een rol te spelen bij psychiatrische aandoeningen, de aandoening zelf en het idee of concept van de aandoening. Deze verschillende objecten interacteren daarbij ook nog met elkaar. Deze interacties kunnen expliciet gemaakt worden door indifferente soorten te onderscheiden van interactieve soorten. Zo wordt duidelijk dat als een aandoening niet gedetermineerd wordt door een biologisch substraat, dit niet automatisch betekent dat zo’n aandoening geheel losstaat van een mensonafhankelijke natuur. CONCLUSIE Hackings filosofie biedt de mogelijkheid om voorbij te gaan aan de tegenstelling tussen de constructivistische positie en de medische kijk op psychiatrische ziekten. BACKGROUND: The constructivist position is often used for psychiatric diseases, in contrast with the general medical view. In the medical view a biological substrate is decisive for a classification as 'disease', which is not the case in the constructivist position. AIM: We investigate how both positions relate to each other in psychiatric diseases. METHOD: Analysis based on a conceptual analysis of Ian Hacking's book The Social Construction of What? (1999). RESULTS: Different objects ought to be distinguished in a constructivist analysis of psychiatric diseases; the disease itself and the idea or concept of that disease. These different objects interact with each other. These interactions can be made explicit by distinguishing interactive kinds from indifferent kinds. Doing so makes it clear that even if a disease is not determined by a biological substrate, this does not imply that a biological substrate is something completely separate from that disease. CONCLUSION: Hacking's philosophy makes it possible to move beyond the opposition between the medical and the constructivist account of psychiatric diseases by combining both accounts

Effects of an 18-week exercise programme started early during breast cancer treatment: a randomised controlled trial

Background: Exercise started shortly after breast cancer diagnosis might prevent or diminish fatigue complaints. The Physical Activity during Cancer Treatment (PACT) study was designed to primarily examine the effects of an 18-week exercise intervention, offered in the daily clinical practice setting and starting within 6 weeks after diagnosis, on preventing an increase in fatigue. Methods: This multi-centre controlled trial randomly assigned 204 breast cancer patients to usual care (n = 102) or supervised aerobic and resistance exercise (n = 102). By design, all patients received chemotherapy between baseline and 18 weeks. Fatigue (i.e., primary outcome at 18 weeks), quality of life, anxiety, depression, and physical fitness were measured at 18 and 36 weeks. Results: Intention-to-treat mixed linear model analyses showed that physical fatigue increased significantly less during cancer treatment in the intervention group compared to control (mean between-group differences at 18 weeks: -1.3; 95 % CI -2.5 to -0.1; effect size -0.30). Results for general fatigue were comparable but did not reach statistical significance (-1.0, 95% CI -2.1; 0.1; effect size -0.23). At 18 weeks, submaximal cardiorespiratory fitness and several muscle strength tests (leg extension and flexion) were significantly higher in the intervention group compared to control, whereas peak oxygen uptake did not differ between groups. At 36 weeks these differences were no longer statistically significant. Quality of life outcomes favoured the exercise group but were not significantly different between groups. Conclusions: A supervised 18-week exercise programme offered early in routine care during adjuvant breast cancer treatment showed positive effects on physical fatigue, submaximal cardiorespiratory fitness, and muscle strength. Exercise early during treatment of breast cancer can be recommended. At 36 weeks, these effects were no longer statistically significant. This might have been caused by the control participants' high physical activity levels during follow-up

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer.

Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC. We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). Patients receiving chemotherapy could cross over to receive nivolumab at the time of disease progression. The primary end point was progression-free survival, as assessed by means of blinded independent central review, among patients with a PD-L1 expression level of 5% or more. Among the 423 patients with a PD-L1 expression level of 5% or more, the median progression-free survival was 4.2 months with nivolumab versus 5.9 months with chemotherapy (hazard ratio for disease progression or death, 1.15; 95% confidence interval [CI], 0.91 to 1.45; P=0.25), and the median overall survival was 14.4 months versus 13.2 months (hazard ratio for death, 1.02; 95% CI, 0.80 to 1.30). A total of 128 of 212 patients (60%) in the chemotherapy group received nivolumab as subsequent therapy. Treatment-related adverse events of any grade occurred in 71% of the patients who received nivolumab and in 92% of those who received chemotherapy. Treatment-related adverse events of grade 3 or 4 occurred in 18% of the patients who received nivolumab and in 51% of those who received chemotherapy. Nivolumab was not associated with significantly longer progression-free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD-L1 expression level of 5% or more. Overall survival was similar between groups. Nivolumab had a favorable safety profile, as compared with chemotherapy, with no new or unexpected safety signals. (Funded by Bristol-Myers Squibb and others; CheckMate 026 ClinicalTrials.gov number, NCT02041533 .)

Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases

Abstract Background Long-term data with immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti-programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and nonsquamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC. Patients and methods Patients were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or discontinuation. The primary end point of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses. Results After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% [95% confidence interval (CI), 14% to 21%] versus 8% (95% CI, 6% to 11%) in the pooled population with squamous or nonsquamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50–0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61–0.81). Rates of treatment-related hepatic adverse events (primarily grade 1–2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%). Conclusions After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated. Clinical trial registration CheckMate 017: NCT01642004; CheckMate 057: NCT01673867

Forests as Commons – Changing Traditions and Governance in Europe

Commons are complex institutions and exist across the world in a wide range of situations regarding locally developed governance and management systems of many different natural resources. For many people commons remain associated with Hardin’s theory concerning the “Tragedy of the Commons” (1968), in which he assumed that local users of a natural resource are unable to formulate governance and management structures concerning their own choices that took into account the long-term sustainability of the resource itself. As a result, Hardin articulated that the tragedy was that the resource would inevitably become degraded in such situations and that the solution was private or public ownership. However, across Europe many forests have for a very long period of time successfully been managed as commons, just as they have in many other parts of the world. This chapter has three main aims: It will provide an introduction to the various types of commons before going on to link the issue of commons to the traditional forest landscapes of Europe, and it will look at how the role of forests and forest landscapes has changed and how it may change further in the future

Calorimetric study of geopolymer binders based on natural pozzolan

This paper investigates the kinetics of geopolymerisation in an inorganic polymeric binder based on a natural pozzolan. The heat released by the exothermic geopolymerisation reaction process is monitored under isothermal temperature conditions, maintained in a differential scanning calorimeter using a water circulation cell. Calorimetric data are obtained isothermally at 65, 75, and 85 °C with various Na2O/Al2O3 and SiO2/Na2O molar ratios and in the presence and absence of small amounts of calcium aluminate cement (used as an efflorescence control admixture in these binder systems). The first stage of reaction, which is rapid and strongly exothermic, is shortened as the temperature increases. The total heat of reaction increases in the mixes containing calcium aluminate cement, but the apparent activation energy calculated using a pseudo-first-order reaction model is lower than without added calcium aluminate cement. At a constant overall SiO2/Na2O molar ratio, the apparent activation energy is decreased as the Na2O/Al2O3 molar ratio increases. Calcium aluminate cement, therefore, reduces the minimum energy required to initiate geopolymerisation reactions of this natural pozzolan and facilitates the progress of the reactions which lead to formation of a cementitious product