The Palomar Kernel Phase Experiment: Testing Kernel Phase Interferometry for Ground-based Astronomical Observations

At present, the principal limitation on the resolution and contrast of astronomical imaging instruments comes from aberrations in the optical path, which may be imposed by the Earth's turbulent atmosphere or by variations in the alignment and shape of the telescope optics. These errors can be corrected physically, with active and adaptive optics, and in post-processing of the resulting image. A recently-developed adaptive optics post-processing technique, called kernel phase interferometry, uses linear combinations of phases that are self-calibrating with respect to small errors, with the goal of constructing observables that are robust against the residual optical aberrations in otherwise well-corrected imaging systems. Here we present a direct comparison between kernel phase and the more established competing techniques, aperture masking interferometry, point spread function (PSF) fitting and bispectral analysis. We resolve the alpha Ophiuchi binary system near periastron, using the Palomar 200-Inch Telescope. This is the first case in which kernel phase has been used with a full aperture to resolve a system close to the diffraction limit with ground-based extreme adaptive optics observations. Excellent agreement in astrometric quantities is found between kernel phase and masking, and kernel phase significantly outperforms PSF fitting and bispectral analysis, demonstrating its viability as an alternative to conventional non-redundant masking under appropriate conditions.Comment: Accepted to MNRA

Unique Resistance of I/LnJ Mice to a Retrovirus Is Due to Sustained Interferon γ–dependent Production of Virus-neutralizing Antibodies

Selection of immune escape variants impairs the ability of the immune system to sustain an efficient antiviral response and to control retroviral infections. Like other retroviruses, mouse mammary tumor virus (MMTV) is not efficiently eliminated by the immune system of susceptible mice. In contrast, MMTV-infected I/LnJ mice are capable of producing IgG2a virus-neutralizing antibodies, sustain this response throughout their life, and secrete antibody-coated virions into the milk, thereby preventing infection of their progeny. Antibodies were produced in response to several MMTV variants and were cross-reactive to them. Resistance to MMTV infection was recessive and was dependent on interferon (IFN)-γ production, because I/LnJ mice with targeted deletion of the INF-γ gene failed to produce any virus-neutralizing antibodies. These findings reveal a novel mechanism of resistance to retroviral infection that is based on a robust and sustained IFN-γ–dependent humoral immune response

The Palomar kernel-phase experiment: testing kernel phase interferometry for ground-based astronomical observations

At present, the principal limitation on the resolution and contrast of astronomical imaging instruments comes from aberrations in the optical path, which may be imposed by the Earth's turbulent atmosphere or by variations in the alignment and shape of the telescope optics. These errors can be corrected physically,with active and adaptive optics, and in post-processing of the resulting image.Arecently developed adaptive optics post-processing technique, called kernelphase interferometry, uses linear combinations of phases that are self-calibrating with respect to small errors, with the goal of constructing observables that are robust against the residual optical aberrations in otherwise well-corrected imaging systems. Here, we present a direct comparison between kernel phase and the more established competing techniques, aperture masking interferometry, point spread function (PSF) fitting and bispectral analysis.We resolve the α Ophiuchi binary system near periastron, using the Palomar 200-Inch Telescope. This is the first case in which kernel phase has been used with a full aperture to resolve a system close to the diffraction limit with ground-based extreme adaptive optics observations. Excellent agreement in astrometric quantities is found between kernel phase and masking, and kernel phase significantly outperforms PSF fitting and bispectral analysis, demonstrating its viability as an alternative to conventional non-redundant masking under appropriate conditions

Emotional and attention-deficit/hyperactivity disorder symptoms of preterm vs. full-term children during COVID-19 pandemic restrictions

BACKGROUND: Preterm children are at higher risk of developing mental health problems than full-term children. Deterioration of children's mental health was observed during COVID-19 pandemic restrictive measures. Our study compared emotional and attention-deficit/hyperactivity disorder (ADHD) symptoms during school closure between preterm and full-term children. METHODS: Data from two French birth cohorts-ELFE and EPIPAGE-2-were used. In 2011, infants born ≥22 weeks' gestation were recruited. Parents completed the Strengths and Difficulties Questionnaire when the children were 9 years old and experiencing school closure. Multivariate multinomial logistic regression models were used. RESULTS: Subjects included 4164 full-term and 1119 preterm children. In univariate analyses, compared to full-term children: extremely and very preterm children more frequently had abnormal and borderline ADHD scores (odds ratio [OR] 1.86, 95% confidence interval [CI] 1.50-2.30, OR 1.42, 95% CI 1.08-1.85, respectively) and abnormal emotional scores (OR 1.86, 95% CI 1.43-2.40); moderate to late preterm children more often had abnormal ADHD scores (OR 1.33, 95% CI 1.01-1.78). The associations did not remain when previous symptoms at 5 years old were considered. CONCLUSIONS: School closure during lockdown did not appear to increase the risk of mental health problems in preterm compared to full-term children. IMPACT STATEMENT: Preterm children are at higher risk of developing mental health problems than full-term children. Deterioration in children's mental health was observed during COVID-19 pandemic restrictions. However, whether preterm children were a particularly vulnerable subgroup during school closure is unclear. In univariate analyses, extremely and very preterm children more often had abnormal and borderline ADHD symptoms and abnormal emotional symptom scores than full-term children. The associations did not remain significantly associated when previous symptoms were considered. Preterm compared to full-term children more often suffer from ADHD and emotional symptoms, but school closure during lockdown did not appear to increase this risk.Santé, perception, pratiques, relations et inégalités sociales en population générale pendant la crise COVID-1

Channelopathies in Cav1.1, Cav1.3, and Cav1.4 voltage-gated L-type Ca2+ channels

Voltage-gated Ca2+ channels couple membrane depolarization to Ca2+-dependent intracellular signaling events. This is achieved by mediating Ca2+ ion influx or by direct conformational coupling to intracellular Ca2+ release channels. The family of Cav1 channels, also termed L-type Ca2+ channels (LTCCs), is uniquely sensitive to organic Ca2+ channel blockers and expressed in many electrically excitable tissues. In this review, we summarize the role of LTCCs for human diseases caused by genetic Ca2+ channel defects (channelopathies). LTCC dysfunction can result from structural aberrations within their pore-forming α1 subunits causing hypokalemic periodic paralysis and malignant hyperthermia sensitivity (Cav1.1 α1), incomplete congenital stationary night blindness (CSNB2; Cav1.4 α1), and Timothy syndrome (Cav1.2 α1; reviewed separately in this issue). Cav1.3 α1 mutations have not been reported yet in humans, but channel loss of function would likely affect sinoatrial node function and hearing. Studies in mice revealed that LTCCs indirectly also contribute to neurological symptoms in Ca2+ channelopathies affecting non-LTCCs, such as Cav2.1 α1 in tottering mice. Ca2+ channelopathies provide exciting disease-related molecular detail that led to important novel insight not only into disease pathophysiology but also to mechanisms of channel function

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Quality indicators for responsible antibiotic use in the inpatient setting: a systematic review followed by an international multidisciplinary consensus procedure

Background This study was conducted as part of the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project and aimed to develop generic quality indicators (QIs) for responsible antibiotic use in the inpatient setting. Methods A RAND-modified Delphi method was applied. First, QIs were identified by a systematic review. A complementary search was performed on web sites of relevant organizations. Duplicates were removed and disease and patient-specific QIs were combined into generic indicators. The relevance of these QIs was appraised by a multidisciplinary international stakeholder panel through two questionnaires and an in-between consensus meeting. Results The systematic review retrieved 70 potential generic QIs. The QIs were appraised by 25 international stakeholders with diverse backgrounds (medical community, public health, patients, antibiotic research and development, regulators, governments). Ultimately, 51 QIs were selected in consensus. QIs with the highest relevance score included: (i) an antibiotic plan should be documented in the medical record at the start of the antibiotic treatment; (ii) the results of bacteriological susceptibility testing should be documented in the medical record; (iii) the local guidelines should correspond to the national guidelines but should be adapted based on local resistance patterns; (iv) an antibiotic stewardship programme should be in place at the healthcare facility; and (v) allergy status should be taken into account when antibiotics are prescribed. Conclusions This systematic and stepwise method combining evidence from literature and stakeholder opinion led to multidisciplinary international consensus on generic inpatient QIs that can be used globally to assess the quality of antibiotic use

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