Marginal Eyespots on Butterfly Wings Deflect Bird Attacks Under Low Light Intensities with UV Wavelengths

Predators preferentially attack vital body parts to avoid prey escape. Consequently, prey adaptations that make predators attack less crucial body parts are expected to evolve. Marginal eyespots on butterfly wings have long been thought to have this deflective, but hitherto undemonstrated function.Here we report that a butterfly, Lopinga achine, with broad-spectrum reflective white scales in its marginal eyespot pupils deceives a generalist avian predator, the blue tit, to attack the marginal eyespots, but only under particular conditions-in our experiments, low light intensities with a prominent UV component. Under high light intensity conditions with a similar UV component, and at low light intensities without UV, blue tits directed attacks towards the butterfly head.In nature, birds typically forage intensively at early dawn, when the light environment shifts to shorter wavelengths, and the contrast between the eyespot pupils and the background increases. Among butterflies, deflecting attacks is likely to be particularly important at dawn when low ambient temperatures make escape by flight impossible, and when insectivorous birds typically initiate another day's search for food. Our finding that the deflective function of eyespots is highly dependent on the ambient light environment helps explain why previous attempts have provided little support for the deflective role of marginal eyespots, and we hypothesize that the mechanism that we have discovered in our experiments in a laboratory setting may function also in nature when birds forage on resting butterflies under low light intensities

The supportive care needs of parents with a child with a rare disease : results of an online survey

Background: Parents caring for a child affected by a rare disease have unmet needs, the origins of which are complex and varied. Our aim was to determine the supportive care needs of parents caring for a child with a rare disease. Methods: An online survey was developed consisting of 45 questions (108 items) and separated into six domains. The survey included questions about perceived level of satisfaction with receiving care, experiences and needs of providing daily care, the impacts of disease on relationships, the emotional and psychological burdens of disease, and parents overall satisfaction with the support received. Results: Three-hundred and one parents from Australia and New Zealand completed the survey; 91 % (n = 275/301) were mothers, with 132 distinct rare diseases being reported. Fifty-four percent (n = 140/259) of parents were dissatisfied with health professionals’ level of knowledge and awareness of disease; 71 % (n = 130/183) of parents felt they received less support compared to other parents. Information regarding present (60 %, n = 146/240) and future services (72 %, n = 174/240) available for their child were considered important. Almost half of parents (45 %, n = 106/236) struggled financially, 38 % (n = 99/236) reduced their working hours and 34 % (n = 79/236) ceased paid employment. Forty-two percent (n = 99/223) of parents had no access to a disease specific support group, and 58 % (n = 134/230) stated that their number of friends had reduced since the birth of their child; 75 % (n = 173/230) had no contact with other parents with a child with a similar disease, and 46 % (n = 106/230) reported feeling socially isolated and desperately lonely. Most frequent emotions expressed by parents in the week prior to completing the survey were anxiety and fear (53 %, n = 119/223), anger and frustration (46 %, n = 103/223) and uncertainty (39 %, n = 88/223). Conclusion: This study is the first to develop an online survey specifically for use with parents to investigate their supportive care needs across a large and diverse group of rare diseases. The findings highlight that parents with a child with a rare disease have common unmet needs regardless of what disease their child has. Such information may allow health providers to improve child outcomes through improving parental supportive care

Improving the effectiveness of psychological interventions for depression and anxiety in the cardiac rehabilitation pathway using group-based metacognitive therapy (PATHWAY Group MCT) : study protocol for a randomised controlled trial

BACKGROUND: Anxiety and depression are prevalent among cardiac rehabilitation patients but pharmacological and psychological treatments have limited effectiveness in this group. Furthermore, psychological interventions have not been systematically integrated into cardiac rehabilitation services despite being a strategic priority for the UK National Health Service. A promising new treatment, metacognitive therapy, may be well-suited to the needs of cardiac rehabilitation patients and has the potential to improve outcomes. It is based on the metacognitive model, which proposes that a thinking style dominated by rumination, worry and threat monitoring maintains emotional distress. Metacognitive therapy is highly effective at reducing this thinking style and alleviating anxiety and depression in mental health settings. This trial aims to evaluate the effectiveness and cost-effectiveness of group-based metacognitive therapy for cardiac rehabilitation patients with elevated anxiety and/or depressive symptoms. METHODS/DESIGN: The PATHWAY Group-MCT trial is a multicentre, two-arm, single-blind, randomised controlled trial comparing the clinical- and cost-effectiveness of group-based metacognitive therapy plus usual cardiac rehabilitation to usual cardiac rehabilitation alone. Cardiac rehabilitation patients (target sample n = 332) with elevated anxiety and/or depressive symptoms will be recruited across five UK National Health Service Trusts. Participants randomised to the intervention arm will receive six weekly sessions of group-based metacognitive therapy delivered by either cardiac rehabilitation professionals or research nurses. The intervention and control groups will both be offered the usual cardiac rehabilitation programme within their Trust. The primary outcome is severity of anxiety and depressive symptoms at 4-month follow-up measured by the Hospital Anxiety and Depression Scale total score. Secondary outcomes are severity of anxiety/depression at 12-month follow-up, health-related quality of life, severity of post-traumatic stress symptoms and strength of metacognitive beliefs at 4- and 12-month follow-up. Qualitative interviews will help to develop an account of barriers and enablers to the effectiveness of the intervention. DISCUSSION: This trial will evaluate the effectiveness and cost-effectiveness of group-based metacognitive therapy in alleviating anxiety and depression in cardiac rehabilitation patients. The therapy, if effective, offers the potential to improve psychological wellbeing and quality of life in this large group of patients. TRIAL REGISTRATION: UK Clinical Trials Gateway, ISRCTN74643496 , Registered on 8 April 2015

Hybrid cosmic ray measurements using the IceAct telescopes in coincidence with the IceCube and IceTop detectors

IceAct is a proposed surface array of compact (50 cm diameter) and cost-effective Imaging Air Cherenkov Telescopes installed at the site of the IceCube Neutrino Observatory at the geographic South Pole. Since January 2019, two IceAct telescope demonstrators, featuring 61 silicon photomultiplier (SiPM) pixels have been taking data in the center of the IceTop surface array during the austral winter. We present the first analysis of hybrid cosmic ray events detected by the IceAct imaging air-Cherenkov telescopes in coincidence with the IceCube Neutrino Observatory, including the IceTop surface array and the IceCube in-ice array. By featuring an energy threshold of about 10 TeV and a wide field-of-view, the IceAct telescopes show promising capabilities of improving current cosmic ray composition studies: measuring the Cherenkov light emissions in the atmosphere adds new information about the shower development not accessible with the current detectors, enabling significantly better primary particle type discrimination on a statistical basis. The hybrid measurement also allows for detailed feasibility studies of detector cross-calibration and of cosmic ray veto capabilities for neutrino analyses. We present the performance of the telescopes, the results from the analysis of two years of data, and an outlook of a hybrid simulation for a future telescope array

Three-year performance of the IceAct telescopes at the IceCube Neutrino Observatory

IceAct is an array of compact Imaging Air Cherenkov Telescopes at the ice surface as part of the IceCube Neutrino Observatory. The telescopes, featuring a camera of 61 silicon photomultipliers and fresnel-lens-based optics, are optimized to be operated in harsh environmental conditions, such as at the South Pole. Since 2019, the first two telescopes have been operating in a stereoscopic configuration in the center of IceCube\u27s surface detector IceTop. With an energy threshold of about 10 TeV and a wide field-of-view, the IceAct telescopes show promising capabilities of improving current cosmic-ray composition studies: measuring the Cherenkov light emissions in the atmosphere adds new information about the shower development not accessible with the current detectors. First simulations indicate that the added information of a single telescope leads, e.g., to an improved discrimination between flux contributions from different primary particle species in the sensitive energy range. We review the performance and detector operations of the telescopes during the past 3 years (2020-2022) and give an outlook on the future of IceAct

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570