CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods

Background: The Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction of genetic variant impact, particularly where relevant to disease. The five complete editions of the CAGI community experiment comprised 50 challenges, in which participants made blind predictions of phenotypes from genetic data, and these were evaluated by independent assessors. // Results: Performance was particularly strong for clinical pathogenic variants, including some difficult-to-diagnose cases, and extends to interpretation of cancer-related variants. Missense variant interpretation methods were able to estimate biochemical effects with increasing accuracy. Assessment of methods for regulatory variants and complex trait disease risk was less definitive and indicates performance potentially suitable for auxiliary use in the clinic. // Conclusions: Results show that while current methods are imperfect, they have major utility for research and clinical applications. Emerging methods and increasingly large, robust datasets for training and assessment promise further progress ahead

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

FUCK YOUR FEELINGS: THE AFFECTIVE WEAPONISATION OF FACTS AND REASON

This paper examines emerging trends in fact signaling: the performative invocation of the idea of Fact and Reason, distinct from the concrete presentation of evidence or reasoning, as a way to cultivate affective solidarity. Emblematic is the conservative influencer Ben Shapiro’s slogan, “facts don’t care about your feelings”: a paean to the mythological figure of emotionlessly objective truth which may then be weaponised against one’s enemies. Scholars are increasingly attentive to the ways in which what was once popularised as a ‘fake news’ epidemic is not simply a virulent strain of bad information in a fundamentally rational online ecosystem, but rather a broader crisis and transformation of what counts as truthful, trustworthy and authentic (e.g. Boler &amp; Davis, 2018; also see Banet-Weiser, 2012). Our contribution emphasises the affective and habitual dimension of this phenomenon. Through a close analysis of Ben Shapiro’s content and personal brand, we show how the generic invocation of Fact and Reason cultivates a sense of affective attachment not defined by ideological consistency or, indeed, the actual practice of research or logical reasoning, but rather a particularly masculinised and adversarial ideal of Truth. The payoff is the reassurance and pleasure of a stable subject position from which one’s political opposition may be Othered with impunity. Facts may not care about your feelings, but insisting upon this fact is all about building a certain structure of feeling.</jats:p

FUCK YOUR FEELINGS: THE AFFECTIVE WEAPONISATION OF FACTS AND REASON

This paper examines emerging trends in fact signaling: the performative invocation of the idea of Fact and Reason, distinct from the concrete presentation of evidence or reasoning, as a way to cultivate affective solidarity. Emblematic is the conservative influencer Ben Shapiro’s slogan, “facts don’t care about your feelings”: a paean to the mythological figure of emotionlessly objective truth which may then be weaponised against one’s enemies. Scholars are increasingly attentive to the ways in which what was once popularised as a ‘fake news’ epidemic is not simply a virulent strain of bad information in a fundamentally rational online ecosystem, but rather a broader crisis and transformation of what counts as truthful, trustworthy and authentic (e.g. Boler &amp; Davis, 2018; also see Banet-Weiser, 2012). Our contribution emphasises the affective and habitual dimension of this phenomenon. Through a close analysis of Ben Shapiro’s content and personal brand, we show how the generic invocation of Fact and Reason cultivates a sense of affective attachment not defined by ideological consistency or, indeed, the actual practice of research or logical reasoning, but rather a particularly masculinised and adversarial ideal of Truth. The payoff is the reassurance and pleasure of a stable subject position from which one’s political opposition may be Othered with impunity. Facts may not care about your feelings, but insisting upon this fact is all about building a certain structure of feeling

A Fully Authenticated Diffie-Hellman Protocol and Its Application in WSNs

The secure authenticated key establishment between nodes in Wireless Sensor Networks (WSNs) has not been fully solved in the existing schemes. It\u27s a good idea to apply the Diffie-Hellman protocol to address it perfectly, but the existing authenticated Diffie-Hellman (ADH) protocols are not perfect because their authentication are partial or delayed. In this paper, we first present a concept of full authentication and propose a new fully authenticated Diffie-Hellman (FADH) prototype with light-certificate-based authentication. And then based on the theory of elliptic curve cryptography, we construct the TinyADH (Tiny Authenticated Diffie-Hellman) protocol with applying the FADH in WSNs. Compared with the existing similar solutions, TinyADH has lower communication overload, is easier to implement into existing standards, and more secure under equivalent computational complexity. The experimental results show that using this scheme for a successful key agreement between two nodes averagely takes about 54 seconds on TelosB. Moreover, the simulation results indicate that repeated key agreement can improve the secure connectivity rate. However, considering the cost performance ratio, it is advisable to take 2 runs of the negotiation

Effects of Exercise on Stress-induced Attenuation of Vaccination Responses in Mice

Studies suggest that exercise can improve vaccination responses in humans. Chronic stress can lead to immunosuppression, and there may be a role for exercise in augmenting immune responses. Purpose To investigate the effects of acute eccentric exercise (ECC) and voluntary wheel exercise training (VWR) on antibody and cell-mediated immune responses to vaccination in chronically stressed mice. We hypothesized that both ECC and VWR would attenuate chronic stress-induced reductions in vaccination responses. Methods Mice were randomized into four groups: control (CON), stress (S)-ECC, S-VWR, and S-sedentary (SED). Stressed groups received chronic restraint stress for 6 h·d-1, 5 d·wk-1 for 3 wk. After the first week of stress, S-ECC were exercised at 17 m·min-1 speed at -20% grade for 45 min on a treadmill and then intramuscularly injected with 100 μg of ovalbumin (OVA) and 200 μg of alum adjuvant. All other groups were also vaccinated at this time. Stress-VWR mice voluntarily ran on a wheel for the entire experiment. Plasma was collected before, and at 1, 2, and 4 wk postvaccination. Enzyme-linked immunosorbent assay was performed to analyze anti-OVA IgG and IgM antibodies. After 3 wk of chronic stress, all mice were injected with OVA into the ear to determine the delayed-type hypersensitivity. Results We found that chronic restraint stress significantly reduced body weight and caused adrenal hypertrophy. We also found both S-ECC and S-VWR groups had significantly elevated anti-OVA IgG (P \u3c 0.05), whereas no significant differences between the two exercise groups. Neither S-ECC nor S-VWR altered anti-OVA IgM or delayed-type hypersensitivity responses compared with S-SED group. Conclusions Acute eccentric exercise and voluntary exercise training alleviated the chronic stress-induced anti-OVA IgG reductions in vaccination responses