Rationale
Memory plays a central role in the psychedelic experience. The spontaneous recall and immersive reliving of autobiographical memories has frequently been noted by researchers and clinicians ...as a salient phenomenon in the profile of subjective effects of classic psychedelic drugs such as psilocybin, LSD, and ayahuasca. The ability for psychedelics to provoke vivid memories has been considered important to their clinical efficacy.
Objective
This review aims to examine and aggregate the findings from experimental, observational, and qualitative studies on the acute modulation of memory by classic psychedelics in humans.
Method
A literature search was conducted using PubMed and PsycInfo as well as manual review of references from eligible studies. Publications reporting quantitative and/or qualitative findings were included; animal studies and case reports were excluded.
Results
Classic psychedelics produce dose-dependently increasing impairments in memory task performance, such that low doses produce no impairment and higher doses produce increasing levels of impairment. This pattern has been observed in tasks assessing spatial and verbal working memory, semantic memory, and non-autobiographical episodic memory. Such impairments may be less pronounced among experienced psychedelic users. Classic psychedelics also increase the vividness of autobiographical memories and frequently stimulate the recall and/or re-experiencing of autobiographical memories, often memories that are affectively intense (positively or negatively valenced) and that had been avoided and/or forgotten prior to the experience.
Conclusions
Classic psychedelics dose-dependently impair memory task performance but may enhance autobiographical memory. These findings are relevant to the understanding of psychological mechanisms of action of psychedelic-assisted psychotherapy.
Objective: Much debate remains regarding why certain countries experience dramatically higher winter mortality. Potential causative factors other than cold exposure have rarely been analysed. ...Comparatively less research exists on excess winter deaths in southern Europe. Multiple time series data on a variety of risk factors are analysed against seasonal-mortality patterns in 14 European countries to identify key relations Subjects and setting: Excess winter deaths (all causes), 1988–97, EU-14. Design: Coefficients of seasonal variation in mortality are calculated for EU-14 using monthly mortality data. Comparable, longitudinal datasets on risk factors pertaining to climate, macroeconomy, health care, lifestyle, socioeconomics, and housing were also obtained. Poisson regression identifies seasonality relations over time. Results: Portugal suffers from the highest rates of excess winter mortality (28%, CI=25% to 31%) followed jointly by Spain (21%, CI=19% to 23%), and Ireland (21%, CI=18% to 24%). Cross country variations in mean winter environmental temperature (regression coefficient (β)=0.27), mean winter relative humidity (β=0.54), parity adjusted per capita national income (β=1.08), per capita health expenditure (β=−1.19), rates of income poverty (β=−0.47), inequality (β=0.97), deprivation (β=0.11), and fuel poverty (β=0.44), and several indicators of residential thermal standards are found to be significantly related to variations in relative excess winter mortality at the 5% level. The strong, positive relation with environmental temperature and strong negative relation with thermal efficiency indicate that housing standards in southern and western Europe play strong parts in such seasonality. Conclusions: High seasonal mortality in southern and western Europe could be reduced through improved protection from the cold indoors, increased public spending on health care, and improved socioeconomic circumstances resulting in more equitable income distribution.
Tumour cells endure both oncogenic and environmental stresses during cancer progression. Transformed cells must meet increased demands for protein and lipid production needed for rapid proliferation ...and must adapt to exist in an oxygen‐ and nutrient‐deprived environment. To overcome such challenges, cancer cells exploit intrinsic adaptive mechanisms such as the unfolded protein response (UPR). The UPR is a pro‐survival mechanism triggered by accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER), a condition referred to as ER stress. IRE1, PERK and ATF6 are three ER anchored transmembrane receptors. Upon induction of ER stress, they signal in a coordinated fashion to re‐establish ER homoeostasis, thus aiding cell survival. Over the past decade, evidence has emerged supporting a role for the UPR in the establishment and progression of several cancers, including breast cancer, prostate cancer and glioblastoma multiforme. This review discusses our current knowledge of the UPR during oncogenesis, tumour growth, metastasis and chemoresistance.
Review: Tumour progression can be broken into distinct stages starting with transformation, leading to unrestricted cell division, angiogenesis, invasion and metastatic spread. Each of these stages present tumour cells with a specific set of challenges, which must be overcome to progress. In this review article we describe the Unfolded Protein Response (UPR) and outline how tumours co‐opt this adaptive cell stress response pathway to ensure their survival and spread.
To paint a fuller picture of economic voters, we combine personal income records with a representative election survey. We examine three central topics in the economic voting literature: pocketbook ...versus sociotropic voting, the effects of partisanship on economic evaluations, and voter myopia. First, we show that voters who appear in survey data to be voting based on the national economy are, in fact, voting equally on the basis of their personal financial conditions. Second, there is strong evidence of both partisan bias and economic information in economic evaluations, but personal economic data is required to separate the two. Third, although in experiments and aggregate historical data recent economic conditions appear to drive vote choice, we find no evidence of myopia when we examine actual personal economic data.
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Tension–compression asymmetry is a notable feature of plasticity in body-centred cubic (bcc) single crystals. Recent experiments reveal striking differences in the plasticity of bcc ...nanopillars for tension and compression. Here we present results from molecular dynamics simulations of nanopillars of bcc Fe in tension and compression. We find that a totally different deformation mechanism applies in each case: dislocation glide in compression and twinning in tension. This difference explains experimentally observed asymmetry in the nanopillar morphology.
In this first-in-human phase 1 study (NCT02964013; MK-7684-001), we investigated the safety and efficacy of the anti-TIGIT (T cell immunoglobulin and ITIM domain) antibody vibostolimab as monotherapy ...or in combination with pembrolizumab.
Part A enrolled patients with advanced solid tumors, and part B enrolled patients with non-small-cell lung cancer (NSCLC). Patients received vibostolimab 2.1-700 mg alone or with pembrolizumab 200 mg in part A and vibostolimab 200 mg alone or with pembrolizumab 200 mg in part B. Primary endpoints were safety and tolerability. Secondary endpoints included pharmacokinetics and objective response rate (ORR) per RECIST v1.1.
Part A enrolled 76 patients (monotherapy, 34; combination therapy, 42). No dose-limiting toxicities were reported. Across doses, 56% of patients receiving monotherapy and 62% receiving combination therapy had treatment-related adverse events (TRAEs); grade 3-4 TRAEs occurred in 9% and 17% of patients, respectively. The most common TRAEs were fatigue (15%) and pruritus (15%) with monotherapy and pruritus (17%) and rash (14%) with combination therapy. Confirmed ORR was 0% with monotherapy and 7% with combination therapy. In part B, 39 patients had anti-PD-1 (programmed cell death protein 1)/PD-L1 (programmed death-ligand 1)-naive NSCLC (all received combination therapy), and 67 had anti-PD-1/PD-L1-refractory NSCLC (monotherapy, 34; combination therapy, 33). In patients with anti-PD-1/PD-L1-naive NSCLC: 85% had TRAEs–the most common were pruritus (38%) and hypoalbuminemia (31%); confirmed ORR was 26%, with responses occurring in both PD-L1-positive and PD-L1-negative tumors. In patients with anti-PD-1/PD-L1-refractory NSCLC: 56% receiving monotherapy and 70% receiving combination therapy had TRAEs–the most common were rash and fatigue (21% each) with monotherapy and pruritus (36%) and fatigue (24%) with combination therapy; confirmed ORR was 3% with monotherapy and 3% with combination therapy.
Vibostolimab plus pembrolizumab was well tolerated and demonstrated antitumor activity in patients with advanced solid tumors, including patients with advanced NSCLC.
•First-in-human phase 1 study in patients with advanced solid tumors who received vibostolimab alone or with pembrolizumab.•Vibostolimab plus pembrolizumab was well tolerated in advanced solid tumors.•Vibostolimab plus pembrolizumab demonstrated antitumor activity in patients with advanced solid tumors.
Does information irrelevant to government performance affect voting behavior? If so, how does this help us understand the mechanisms underlying voters' retrospective assessments of candidates' ...performance in office? To precisely test for the effects of irrelevant information, we explore the electoral impact of local college football games just before an election, irrelevant events that government has nothing to do with and for which no government response would be expected. We find that a win in the 10 d before Election Day causes the incumbent to receive an additional 1.61 percentage points of the vote in Senate, gubernatorial, and presidential elections, with the effect being larger for teams with stronger fan support. In addition to conducting placebo tests based on postelection games, we demonstrate these effects by using the betting market's estimate of a team's probability of winning the game before it occurs to isolate the surprise component of game outcomes. We corroborate these aggregate-level results with a survey that we conducted during the 2009 NCAA men's college basketball tournament, where we find that surprising wins and losses affect presidential approval. An experiment embedded within the survey also indicates that personal well-being may influence voting decisions on a subconscious level. We find that making people more aware of the reasons for their current state of mind reduces the effect that irrelevant events have on their opinions. These findings underscore the subtle power of irrelevant events in shaping important real-world decisions and suggest ways in which decision making can be improved.
A novel in situ IR spectroscopic approach is demonstrated for the characterization of hydrogenase during catalytic turnover. E. coli hydrogenase 1 (Hyd‐1) is adsorbed on a high surface‐area carbon ...electrode and subjected to the same electrochemical control and efficient supply of substrate as in protein film electrochemistry during spectral acquisition. The spectra reveal that the active site state known as Ni‐L, observed in other NiFe hydrogenases only under illumination or at cryogenic temperatures, can be generated reversibly in the dark at ambient temperature under both turnover and non‐turnover conditions. The observation that Ni‐L is present at all potentials during turnover under H2 suggests that the final steps in the catalytic cycle of H2 oxidation by Hyd‐1 involve sequential proton and electron transfer via Ni‐L. A broadly applicable IR spectroscopic technique is presented for addressing electrode‐adsorbed redox enzymes under fast catalytic turnover.
Protein film IR electrochemistry: A combination of precise electrochemical control with infrared spectral acquisition provides fresh insight into catalytic states of the NiFe hydrogenase active site.
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