Extreme magnification of an individual star at redshift 1.5 by a galaxy-cluster lens

Galaxy-cluster gravitational lenses can magnify background galaxies by a total factor of up to ~50. Here we report an image of an individual star at redshift z = 1.49 (dubbed MACS J1149 Lensed Star 1) magnified by more than ×2,000. A separate image, detected briefly 0.26″ from Lensed Star 1, is probably a counterimage of the first star demagnified for multiple years by an object of ≳3 solar masses in the cluster. For reasonable assumptions about the lensing system, microlensing fluctuations in the stars’ light curves can yield evidence about the mass function of intracluster stars and compact objects, including binary fractions and specific stellar evolution and supernova models. Dark-matter subhaloes or massive compact objects may help to account for the two images’ long-term brightness ratio

Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: A prospective observational study

Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with =2 clinical signs/symptoms of NP-C were considered ''suspected NP-C'' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI =70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores =70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Early health system responses to the COVID-19 pandemic in Mediterranean countries: A tale of successes and challenges

This paper conducts a comparative review of the (curative) health systems’ response taken by Cyprus, Greece, Israel, Italy, Malta, Portugal, and Spain during the first six months of the COVID-19 pandemic. Prior to the COVID-19 pandemic, these Mediterranean countries shared similarities in terms of health system resources, which were low compared to the EU/OECD average. We distill key policy insights regarding the governance tools adopted to manage the pandemic, the means to secure sufficient physical infrastructure and workforce capacity and some financing and coverage aspects. We performed a qualitative analysis of the evidence reported to the ‘Health System Response Monitor’ platform of the European Observatory by country experts. We found that governance in the early stages of the pandemic was undertaken centrally in all the Mediterranean countries, even in Italy and Spain where regional authorities usually have autonomy over health matters. Stretched public resources prompted countries to deploy “flexible” intensive care unit capacity and health workforce resources as agile solutions. The private sector was also utilized to expand resources and health workforce capacity, through special public-private partnerships. Countries ensured universal coverage for COVID-19-related services, even for groups not usually entitled to free publicly financed health care, such as undocumented migrants. We conclude that flexibility, speed and adaptive management in health policy responses were key to responding to immediate needs during the COVID-19 pandemic. Financial barriers to accessing care as well as potentially higher mortality rates were avoided in most of the countries during the first wave. Yet it is still early to assess to what extent countries were able to maintain essential services without undermining equitable access to high quality care. © 202

Balancing financial incentives during COVID-19: a comparison of provider payment adjustments across 20 countries.

Objective Provider payment mechanisms were adjusted in many countries in response to the COVID-19 pandemic in 2020. Our objective was to review adjustments for hospitals and healthcare professionals across 20 countries. Method We developed an analytical framework distinguishing between payment adjustments compensating income loss and those covering extra costs related to COVID-19. Information was extracted from the Covid-19 Health System Response Monitor (HSRM) and classified according to the framework. Findings We found that income loss was not a problem in countries where professionals were paid by salary or capitation and hospitals received global budgets. In countries where payment was based on activity, income loss was compensated through budgets and higher fees. New FFS payments were introduced to incentivize remote services. Payments for COVID-19 related costs included new fees for out- and inpatient services but also new PD and DRG tariffs for hospitals. Budgets covered the costs of adjusting wards, creating new (ICU) beds, and hiring staff. Conclusions We conclude that public payers assumed most of the COVID-19-related financial risk. In view of future pandemics policymakers should work to increase resilience of payment systems by: (1) having systems in place to rapidly adjust payment systems; (2) being aware of the economic incentives created by these adjustments such as cost-containment or increasing the number of patients or services, that can result in unintended consequences such as risk selection or overprovision of care; and (3) periodically evaluating the effects of payment adjustments on access and quality of care

Extreme magnification of an individual star at redshift 1.5 by a galaxy-cluster lens

Galaxy-cluster gravitational lenses can magnify background galaxies by a total factor of up to ~50. Here we report an image of an individual star at redshift z = 1.49 (dubbed MACS J1149 Lensed Star 1) magnified by more than 72,000. A separate image, detected briefly 0.26\u2033 from Lensed Star 1, is probably a counterimage of the first star demagnified for multiple years by an object of 733 solar masses in the cluster. For reasonable assumptions about the lensing system, microlensing fluctuations in the stars' light curves can yield evidence about the mass function of intracluster stars and compact objects, including binary fractions and specific stellar evolution and supernova models. Dark-matter subhaloes or massive compact objects may help to account for the two images' long-term brightness ratio

Genome-wide association analysis identifies susceptibility loci for migraine without aura

peer reviewedMigraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 x 10(-5) for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 x 10(-4); combined P = 7.06 x 10(-11)) and at 3p24 (near TGFBR2; replication P = 1.0 x 10(-4); combined P = 1.17 x 10(-9)). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 x 10(-8) and P = 0.02; combined P = 3.86 x 10(-8), respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder