Self-esteem depends on beliefs about the rate of change of social approval

A major challenge in understanding the neurobiological basis of psychiatric disorders is rigorously quantifying subjective metrics that lie at the core of mental illness, such as low self-esteem. Self-esteem can be conceptualized as a ‘gauge of social approval’ that increases in response to approval and decreases in response to disapproval. Computational studies have shown that learning signals that represent the difference between received and expected social approval drive changes in self-esteem. However, it is unclear whether self-esteem based on social approval should be understood as a value updated through associative learning, or as a belief about approval, updated by new evidence depending on how strongly it is held. Our results show that belief-based models explain self-esteem dynamics in response to social evaluation better than associative learning models. Importantly, they suggest that in the short term, self-esteem signals the direction and rate of change of one’s beliefs about approval within a group, rather than one’s social position

Discounting Future Reward in an Uncertain World

Humans discount delayed relative to more immediate reward. A plausible explanation is that impatience arises partly from uncertainty, or risk, implicit in delayed reward. Existing theories of discounting-as-risk focus on a probability that delayed reward will not materialize. By contrast, we examine how uncertainty in the magnitude of delayed reward contributes to delay discounting. We propose a model wherein reward is discounted proportional to the rate of random change in its magnitude across time, termed volatility. We find evidence to support this model across three experiments (total N = 158). First, using a task where participants chose when to sell products, whose price dynamics they previously learned, we show discounting increases in line with price volatility. Second, we show that this effect pertains over naturalistic delays of up to 4 months. Using functional magnetic resonance imaging, we observe a volatility-dependent decrease in functional hippocampal–prefrontal coupling during intertemporal choice. Third, we replicate these effects in a larger online sample, finding that volatility discounting within each task correlates with baseline discounting outside of the task.We conclude that delay discounting partly reflects time-dependent uncertainty about reward magnitude, that is volatility. Our model captures how discounting adapts to volatility, thereby partly accounting for individual differences in impatience. Our imaging findings suggest a putative mechanism whereby uncertainty reduces prospective simulation of future outcomes

Diagnosis of common health conditions among autistic adults in the UK: evidence from a matched cohort study

Background: Autistic people are disproportionately likely to experience premature mortality and most mental and physical health conditions. We measured the incidence of diagnosed conditions accounting for the most disability-adjusted life years in the UK population according to the Global Burden of Disease study (anxiety, depression, self-harm, harmful alcohol use, substance use, migraine, neck or back pain, and gynaecological conditions). Methods Participants were aged 18 years or above and had an autism diagnosis recorded in the IQVIA Medical Research Database between 01/01/2000 and 16/01/2019. We included 15,675 autistic adults without intellectual disability, 6437 autistic adults with intellectual disability, and a comparison group matched (1:10) by age, sex, and primary care practice. We estimated crude incidences and incidence rate ratios (IRRs) adjusted for age and sex. Findings Autistic adults without intellectual disability experienced a higher incidence (IRR, 95% CI) of self-harm (2.07, 1.79–2.40), anxiety (1.91, 1.76–2.06), depressive disorders (1.79, 1.67–1.92), and substance use (1.24, 1.02–1.51) relative to comparison participants. Incidences of harmful alcohol use (1.01, 0.85–1.18), migraine (0.99, 0.84–1.17), and gynaecological conditions (1.19, 0.95–1.49) did not differ. Neck or back pain incidence was lower (0.88, 0.82–0.95). Autistic adults with intellectual disability experienced a higher incidence of self-harm (2.08, 1.69–2.56). Incidences of anxiety (1.14, 1.00–1.30), gynaecological conditions (1.22, 0.93–1.62), and substance use (1.08, 0.80–1.47) did not differ, and lower incidences were found for depressive disorders (0.73, 0.64–0.83), harmful alcohol use (0.65, 0.50–0.84), migraine (0.55, 0.42–0.74), and neck or back pain (0.49, 0.44–0.55). Interpretation Although our findings cannot be directly compared to previous prevalence studies, they contrast with the higher frequency of mental and physical health conditions in autistic adults reported in studies that directly assessed and/or surveyed autistic people about co-occurring conditions. The present findings may suggest under-diagnosis of common conditions in autistic people, particularly those with intellectual disability. Improved detection should be a clinical and policy priority to reduce health inequalities

Estimating life expectancy and years of life lost for autistic people in the UK: a matched cohort study

Background: Previous research has shown that people who have been diagnosed autistic are more likely to die prematurely than the general population. However, statistics on premature mortality in autistic people have often been misinterpreted. In this study we aimed to estimate the life expectancy and years of life lost experienced by autistic people living in the UK.// Methods: We studied people in the IQVIA Medical Research Database with an autism diagnosis between January 1, 1989 and January 16, 2019. For each participant diagnosed autistic, we included ten comparison participants without an autism diagnosis, matched by age, sex, and primary care practice. We calculated age- and sex-standardised mortality ratios comparing people diagnosed autistic to the reference group. We used Poisson regression to estimate age-specific mortality rates, and life tables to estimate life expectancy at age 18 and years of life lost. We analysed the data separately by sex, and for people with and without a record of intellectual disability. We discuss the findings in the light of the prevalence of recorded diagnosis of autism in primary care compared to community estimates.// Findings: From a cohort of nearly 10 million people, we identified 17,130 participants diagnosed autistic without an intellectual disability (matched with 171,300 comparison participants), and 6450 participants diagnosed autistic with an intellectual disability (matched with 64,500 comparison participants). The apparent estimates indicated that people diagnosed with autism but not intellectual disability had 1.71 (95% CI: 1.39–2.11) times the mortality rate of people without these diagnoses. People diagnosed with autism and intellectual disability had 2.83 (95% CI: 2.33–3.43) times the mortality rate of people without these diagnoses. Likewise, the apparent reduction in life expectancy for people diagnosed with autism but not intellectual disability was 6.14 years (95% CI: 2.84–9.07) for men and 6.45 years (95% CI: 1.37–11.58 years) for women. The apparent reduction in life expectancy for people diagnosed with autism and intellectual disability was 7.28 years (95% CI: 3.78–10.27) for men and 14.59 years (95% CI: 9.45–19.02 years) for women. However, these findings are likely to be subject to exposure misclassification biases: very few autistic adults and older-adults have been diagnosed, meaning that we could only study a fraction of the total autistic population. Those who have been diagnosed may well be those with greater support needs and more co-occurring health conditions than autistic people on average

Deep seabed mining: A note on some potentials and risks to the sustainable mineral extraction from the oceans

The rapidly increasing global populations and socio-economic development in the Global South have resulted in rising demand for natural resources. There are many plans for harvesting natural resources from the ocean floor, especially rare metals and minerals. However, if proper care is not taken, there is substantial potential for long-lasting and even irreversible physical and environmental impacts on the deep-sea ecosystems, including on biodiversity and ecosystem functioning. This paper reviews the literature on some potentials and risks to deep seabed mining (DSM), outlining its legal aspects and environmental impacts. It presents two case studies that describe the environmental risks related to this exploitative process. They include significant disturbance of the seabed, light and noise pollution, the creation of plumes, and negative impacts on the surface, benthic, and meso-and bathypelagic zones. The study suggests some of the issues interested companies should consider in preventing the potential physical and environmental damages DSM may cause. Sustainable mining and the use of minerals are vital in meeting various industrial demands

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

An internal ribosome entry site in the 5′ untranslated region of epidermal growth factor receptor allows hypoxic expression

The expression of epidermal growth factor receptor (EGFR/ERBB1/HER1) is implicated in the progress of numerous cancers, a feature that has been exploited in the development of EGFR antibodies and EGFR tyrosine kinase inhibitors as anti-cancer drugs. However, EGFR also has important normal cellular functions, leading to serious side effects when EGFR is inhibited. One damaging characteristic of many oncogenes is the ability to be expressed in the hypoxic conditions associated with the tumour interior. It has previously been demonstrated that expression of EGFR is maintained in hypoxic conditions via an unknown mechanism of translational control, despite global translation rates generally being attenuated under hypoxic conditions. In this report, we demonstrate that the human EGFR 5′ untranslated region (UTR) sequence can initiate the expression of a downstream open reading frame via an internal ribosome entry site (IRES). We show that this effect is not due to either cryptic promoter activity or splicing events. We have investigated the requirement of the EGFR IRES for eukaryotic initiation factor 4A (eIF4A), which is an RNA helicase responsible for processing RNA secondary structure as part of translation initiation. Treatment with hippuristanol (a potent inhibitor of eIF4A) caused a decrease in EGFR 5′ UTR-driven reporter activity and also a reduction in EGFR protein level. Importantly, we show that expression of a reporter gene under the control of the EGFR IRES is maintained under hypoxic conditions despite a fall in global translation rates

A Novel High-Throughput Assay for Islet Respiration Reveals Uncoupling of Rodent and Human Islets

The pancreatic beta cell is unique in its response to nutrient by increased fuel oxidation. Recent studies have demonstrated that oxygen consumption rate (OCR) may be a valuable predictor of islet quality and long term nutrient responsiveness. To date, high-throughput and user-friendly assays for islet respiration are lacking. The aim of this study was to develop such an assay and to examine bioenergetic efficiency of rodent and human islets.The XF24 respirometer platform was adapted to islets by the development of a 24-well plate specifically designed to confine islets. The islet plate generated data with low inter-well variability and enabled stable measurement of oxygen consumption for hours. The F1F0 ATP synthase blocker oligomycin was used to assess uncoupling while rotenone together with myxothiazol/antimycin was used to measure the level of non-mitochondrial respiration. The use of oligomycin in islets was validated by reversing its effect in the presence of the uncoupler FCCP. Respiratory leak averaged to 59% and 49% of basal OCR in islets from C57Bl6/J and FVB/N mice, respectively. In comparison, respiratory leak of INS-1 cells and C2C12 myotubes was measured to 38% and 23% respectively. Islets from a cohort of human donors showed a respiratory leak of 38%, significantly lower than mouse islets.The assay for islet respiration presented here provides a novel tool that can be used to study islet mitochondrial function in a relatively high-throughput manner. The data obtained in this study shows that rodent islets are less bioenergetically efficient than human islets as well as INS1 cells

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40