Phases of matter are usually identified through spontaneous symmetry breaking, especially regarding unconventional superconductivity and the interactions from which it originates. In that context, ...the superconducting state of the quasi-two-dimensional and strongly correlated perovskite Sr2RuO4 is considered to be the only solid-state analogue to the superfluid 3He-A phase, with an odd-parity order parameter that is unidirectional in spin space for all electron momenta and breaks time-reversal symmetry. This characterization was recently called into question by a search for an expected 'split' transition in a Sr2RuO4 crystal under in-plane uniaxial pressure, which failed to find any such evidence; instead, a dramatic rise and a peak in a single-transition temperature were observed. Here we use nuclear magnetic resonance (NMR) spectroscopy of oxygen-17, which is directly sensitive to the order parameter via hyperfine coupling to the electronic spin degrees of freedom, to probe the nature of superconductivity in Sr2RuO4 and its evolution under strain. A reduction of the Knight shift is observed for all strain values and at temperatures below the critical temperature, consistent with a drop in spin polarization in the superconducting state. In unstrained samples, our results contradict a body of previous NMR work reporting no change in the Knight shift and the most prevalent theoretical interpretation of the order parameter as a chiral p-wave state. Sr2RuO4 is an extremely clean layered perovskite and its superconductivity emerges from a strongly correlated Fermi liquid, and our work imposes tight constraints on the order parameter symmetry of this archetypal system.
This study evaluated the association of time in range (TIR) of 70-180 mg/dL (3.9-10 mmol/L) with the development or progression of retinopathy and development of microalbuminuria using the Diabetes ...Control and Complications Trial (DCCT) data set in order to validate the use of TIR as an outcome measure for clinical trials.
In the DCCT, blood glucose concentrations were measured at a central laboratory from seven fingerstick samples (seven-point testing: pre- and 90-min postmeals and at bedtime) collected during 1 day every 3 months. Retinopathy progression was assessed every 6 months and urinary microalbuminuria development every 12 months. Proportional hazards models were used to assess the association of TIR and other glycemic metrics, computed from the seven-point fingerstick data, with the rate of development of microvascular complications.
Mean TIR of seven-point profiles for the 1,440 participants was 41 ± 16%. The hazard rate of development of retinopathy progression was increased by 64% (95% CI 51-78), and development of the microalbuminuria outcome was increased by 40% (95% CI 25-56), for each 10 percentage points lower TIR (
< 0.001 for each). Results were similar for mean glucose and hyperglycemia metrics.
Based on these results, a compelling case can be made that TIR is strongly associated with the risk of microvascular complications and should be an acceptable end point for clinical trials. Although hemoglobin A
remains a valuable outcome metric in clinical trials, TIR and other glycemic metrics-especially when measured with continuous glucose monitoring-add value as outcome measures in many studies.
Objective
To describe the prevalence of maternal depression from pregnancy to 4 years postpartum, and the risk factors for depressive symptoms at 4 years postpartum.
Design
Prospective pregnancy ...cohort study of nulliparous women.
Setting
Melbourne, Australia.
Sample
In all, 1507 women completed baseline data in pregnancy (mean gestation 15 weeks).
Methods
Women were recruited from six public hospitals. Questionnaires were completed at recruitment and 3, 6, 12 and 18 months postpartum, and 4 years postpartum.
Main outcome measures
Scores ≥13 on the Edinburgh Postnatal Depression Scale were used to indicate depressive symptoms.
Results
Almost one in three women reported depressive symptoms at least once in the first 4 years after birth. The prevalence of depressive symptoms at 4 years postpartum was 14.5%, and was higher than at any time‐point in the first 12 months postpartum. Women with one child at 4 years postpartum were more likely to report depressive symptoms at this time compared with women with subsequent children (22.9 versus 11.3%), and this association remained significant in adjusted models (Adjusted odds ratio 1.71, 95% confidence interval 1.12–2.63).
Conclusions
Maternal depression is more common at 4 years postpartum than at any time in the first 12 months postpartum, and women with one child at 4 years postpartum report significantly higher levels of depressive symptoms than women with subsequent children. There is a need for scaling up of current services to extend surveillance of maternal mental health to cover the early years of parenting.
Animals experience varying levels of predation risk as they navigate heterogeneous landscapes, and behavioral responses to perceived risk can structure ecosystems. The concept of the landscape of ...fear has recently become central to describing this spatial variation in risk, perception, and response. We present a framework linking the landscape of fear, defined as spatial variation in prey perception of risk, to the underlying physical landscape and predation risk, and to resulting patterns of prey distribution and antipredator behavior. By disambiguating the mechanisms through which prey perceive risk and incorporate fear into decision making, we can better quantify the nonlinear relationship between risk and response and evaluate the relative importance of the landscape of fear across taxa and ecosystems.
Recent technological advances have provided unprecedented insights into the movement and behavior of animals on heterogeneous landscapes. Some studies have indicated that spatial variation in predation risk plays a major role in prey decision making, which can ultimately structure ecosystems.
The concept of the ‘landscape of fear’ was introduced in 2001 and has been widely adopted to describe spatial variation predation risk, risk perception, and response. However, increasingly divergent interpretations of its meaning and application now cloud understanding and synthesis, and at least 15 distinct processes and states have been described as landscapes of fear.
Here, we refocus the definition of the landscape of fear as an animal’s perception of spatial variation in predation risk.
Predation risk, the landscape of fear, and prey antipredator responses map imperfectly onto each other, due to ecological constraints and trade-offs.
The relative importance of the landscape of fear in shaping population dynamics and species interactions varies across systems, and human activity is altering and creating new landscapes of fear for wild animals.
Increased concentrations of atmospheric greenhouse gases have led to a global mean surface temperature 1.0°C higher than during the pre-industrial period. We expand on the recent IPCC Special Report ...on global warming of 1.5°C and review the additional risks associated with higher levels of warming, each having major implications for multiple geographies, climates, and ecosystems. Limiting warming to 1.5°C rather than 2.0°C would be required to maintain substantial proportions of ecosystems and would have clear benefits for human health and economies. These conclusions are relevant for people everywhere, particularly in low- and middle-income countries, where the escalation of climate-related risks may prevent the achievement of the United Nations Sustainable Development Goals.
Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality
. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated ...liver disease. The gut microbiota promotes ethanol-induced liver disease in mice
, but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin-a two-subunit exotoxin that is secreted by Enterococcus faecalis
-as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis.
Summary Most patients requiring midface reconstruction have had ablative surgery for malignant disease, and most require postoperative radiotherapy. This type of facial reconstruction attracts ...controversy, not only because of the many reconstructive options, but also because dental and facial prostheses can be very successful in selected cases. This Personal View is based on a new classification of the midface defect, which emphasises the increasing complexity of the problem. Low defects not involving the orbital adnexae can often be successfully treated with dental obturators. For the more extensive maxillary defects, there is consensus that a free flap is required. Composite flaps of bone and muscle harvested from the iliac crest with internal oblique or the scapula tip with latissimus dorsi can more reliably support the orbit and cheek than soft-tissue free flaps and non-vascularised grafts, and also enable an implant-borne dental or orbital prosthesis. Nasomaxillary defects usually require bone to augment the loss of the nasal bones, but orbitomaxillary cases can be managed more simply with local or soft-tissue free flaps. We review the current options and our own experience over the past 15 years in an attempt to rationalise the management of these defects.
Mixed lineage kinase domain-like pseudokinase (MLKL) mediates necroptosis by translocating to the plasma membrane and inducing its rupture. The activation of MLKL occurs in a multimolecular complex ...(the 'necrosome'), which is comprised of MLKL, receptor-interacting serine/threonine kinase (RIPK)-3 (RIPK3) and, in some cases, RIPK1. Within this complex, RIPK3 phosphorylates the activation loop of MLKL, promoting conformational changes and allowing the formation of MLKL oligomers, which migrate to the plasma membrane. Previous studies suggested that RIPK3 could phosphorylate the murine MLKL activation loop at Ser345, Ser347 and Thr349. Moreover, substitution of the Ser345 for an aspartic acid creates a constitutively active MLKL, independent of RIPK3 function. Here we examine the role of each of these residues and found that the phosphorylation of Ser345 is critical for RIPK3-mediated necroptosis, Ser347 has a minor accessory role and Thr349 seems to be irrelevant. We generated a specific monoclonal antibody to detect phospho-Ser345 in murine cells. Using this antibody, a series of MLKL mutants and a novel RIPK3 inhibitor, we demonstrate that the phosphorylation of Ser345 is not required for the interaction between RIPK3 and MLKL in the necrosome, but is essential for MLKL translocation, accumulation in the plasma membrane, and consequent necroptosis.
Silver nanoparticles have antibacterial properties, but their use has been a cause for concern because they persist in the environment. Here, we show that lignin nanoparticles infused with silver ...ions and coated with a cationic polyelectrolyte layer form a biodegradable and green alternative to silver nanoparticles. The polyelectrolyte layer promotes the adhesion of the particles to bacterial cell membranes and, together with silver ions, can kill a broad spectrum of bacteria, including Escherichia coli, Pseudomonas aeruginosa and quaternary-amine-resistant Ralstonia sp. Ion depletion studies have shown that the bioactivity of these nanoparticles is time-limited because of the desorption of silver ions. High-throughput bioactivity screening did not reveal increased toxicity of the particles when compared to an equivalent mass of metallic silver nanoparticles or silver nitrate solution. Our results demonstrate that the application of green chemistry principles may allow the synthesis of nanoparticles with biodegradable cores that have higher antimicrobial activity and smaller environmental impact than metallic silver nanoparticles.
The duration and effectiveness of immunity from infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relevant to pandemic policy interventions, ...including the timing of vaccine boosters.
We investigated the duration and effectiveness of immunity in a prospective cohort of asymptomatic health care workers in the United Kingdom who underwent routine polymerase-chain-reaction (PCR) testing. Vaccine effectiveness (≤10 months after the first dose of vaccine) and infection-acquired immunity were assessed by comparing the time to PCR-confirmed infection in vaccinated persons with that in unvaccinated persons, stratified according to previous infection status. We used a Cox regression model with adjustment for previous SARS-CoV-2 infection status, vaccine type and dosing interval, demographic characteristics, and workplace exposure to SARS-CoV-2.
Of 35,768 participants, 27% (9488) had a previous SARS-CoV-2 infection. Vaccine coverage was high: 95% of the participants had received two doses (78% had received BNT162b2 vaccine Pfizer-BioNTech with a long interval between doses, 9% BNT162b2 vaccine with a short interval between doses, and 8% ChAdOx1 nCoV-19 vaccine AstraZeneca). Between December 7, 2020, and September 21, 2021, a total of 2747 primary infections and 210 reinfections were observed. Among previously uninfected participants who received long-interval BNT162b2 vaccine, adjusted vaccine effectiveness decreased from 85% (95% confidence interval CI, 72 to 92) 14 to 73 days after the second dose to 51% (95% CI, 22 to 69) at a median of 201 days (interquartile range, 197 to 205) after the second dose; this effectiveness did not differ significantly between the long-interval and short-interval BNT162b2 vaccine recipients. At 14 to 73 days after the second dose, adjusted vaccine effectiveness among ChAdOx1 nCoV-19 vaccine recipients was 58% (95% CI, 23 to 77) - considerably lower than that among BNT162b2 vaccine recipients. Infection-acquired immunity waned after 1 year in unvaccinated participants but remained consistently higher than 90% in those who were subsequently vaccinated, even in persons infected more than 18 months previously.
Two doses of BNT162b2 vaccine were associated with high short-term protection against SARS-CoV-2 infection; this protection waned considerably after 6 months. Infection-acquired immunity boosted with vaccination remained high more than 1 year after infection. (Funded by the U.K. Health Security Agency and others; ISRCTN Registry number, ISRCTN11041050.).
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